RESUMO
BACKGROUND: The most common chronic complication of preterm birth is bronchopulmonary dysplasia (BPD), widely referred to as chronic lung disease of prematurity. All current definitions rely on characterizing the disease based on respiratory support level and do not provide full understanding of the underlying cardiopulmonary pathophysiology. OBJECTIVE: To evaluate a rapid functional lung imaging technique in premature infants and to quantitate pulmonary ventilation using 1.5 Tesla magnetic resonance imaging (MRI). MATERIALS AND METHODS: We conducted a prospective MRI study of 12 premature infants in the neonatal intensive care unit (NICU) using the phase resolved functional lung MRI technique to calculate pulmonary ventilation parameters in preterm infants with and without BPD grade 0/1 (n = 6) and grade 2/3 (n = 6). RESULTS: The total ventilation defect percentage showed a significant difference between groups (16.0% IQR (11.0%,18%) BPD grade 2/3 vs. 8.0% IQR (4.5%,9.0%) BPD grade 0/1, p = 0.01). CONCLUSION: Phase-resolved functional lung MRI is feasible for assessment of ventilation defect percentages in preterm infants and shows regional variation in localized lung function in this population.
Assuntos
Displasia Broncopulmonar , Nascimento Prematuro , Lactente , Feminino , Recém-Nascido , Humanos , Recém-Nascido Prematuro , Displasia Broncopulmonar/diagnóstico por imagem , Estudos Prospectivos , Pulmão/patologia , Imageamento por Ressonância Magnética/métodosRESUMO
OBJECTIVE: The hypothesis of this study is that human subchondral bone exhibits abnormal patterns of perfusion in osteoarthritis (OA) that can be characterized by kinetic parameters of blood flow using dynamic contrast enhanced (DCE) MRI. DESIGN: Fifteen subjects with advanced OA of the knee and seven control subjects without OA were studied at 1.5 T with DCE-MRI. Region of interest (ROIs) analysis of pharmacokinetic perfusion parameters were used to examine initial uptake and washout of the contrast agent in the lateral tibial plateau. RESULTS: Arterial and venous perfusion kinetics were abnormal in subchondral OA bone compared to those of normal controls. Time-intensity curves (TIC) exhibited delayed contrast clearance in OA knees compared to normal. Quantitatively, changes were observed in the kinetic parameters, kep, Akep, and kel. The mean kep and Akep were reduced in OA, compared to normal bone, indicating a reduction of arterial inflow and delayed signal enhancement. The kel in OA bone was lower than in normal bone, the negative kel indicating a reduction in venous outflow. The area under the TIC (AUC60) indicated greater residual contrast in OA bone. CONCLUSIONS: DCE-MRI can quantitatively assess subchondral bone perfusion kinetics in human OA and identify heterogeneous regions of perfusion deficits. The results are consistent with venous stasis in OA, reflecting venous outflow obstruction, and can affect intraosseous pressure, reduce arterial inflow, reduce oxygen content, and may contribute to altered cell signaling in, and the pathophysiology of, OA.
Assuntos
Meios de Contraste , Imagem de Difusão por Ressonância Magnética/métodos , Articulação do Joelho/irrigação sanguínea , Osteoartrite do Joelho/diagnóstico por imagem , Idoso , Fenômenos Biomecânicos , Velocidade do Fluxo Sanguíneo , Osso e Ossos/irrigação sanguínea , Estudos de Casos e Controles , Feminino , Humanos , Articulação do Joelho/fisiopatologia , Masculino , Pessoa de Meia-Idade , Osteoartrite do Joelho/patologia , Valores de Referência , Índice de Gravidade de DoençaRESUMO
BACKGROUND AND PURPOSE: The choroid plexus (CP) within the brain ventricles is well-known to produce cerebrospinal fluid (CSF). Recently, the CP has been recognized as critical in modulating inflammation. MRI-measured CP enlargement has been reported in neuroinflammatory disorders like MS as well as with aging and neurodegeneration. The basis of MRI-measured CP enlargement is unknown. On the basis of tissue studies demonstrating CP calcification as a common pathology associated with aging and disease, we hypothesized that previously unmeasured CP calcification contributes to MRI-measured CP volume and may be more specifically associated with neuroinflammation. MATERIALS AND METHODS: We analyzed 60 subjects (43 healthy controls and 17 subjects with Parkinson's disease) who underwent PET/CT using 11C-PK11195, a radiotracer sensitive to the translocator protein expressed by activated microglia. Cortical inflammation was quantified as nondisplaceable binding potential. Choroid plexus calcium was measured via manual tracing on low-dose CT acquired with PET and automatically using a new CT/MRI method. Linear regression assessed the contribution of choroid plexus calcium, age, diagnosis, sex, overall volume of the choroid plexus, and ventricle volume to cortical inflammation. RESULTS: Fully automated choroid plexus calcium quantification was accurate (intraclass correlation coefficient with manual tracing = .98). Subject age and choroid plexus calcium were the only significant predictors of neuroinflammation. CONCLUSIONS: Choroid plexus calcification can be accurately and automatically quantified using low-dose CT and MRI. Choroid plexus calcification-but not choroid plexus volume-predicted cortical inflammation. Previously unmeasured choroid plexus calcium may explain recent reports of choroid plexus enlargement in human inflammatory and other diseases. Choroid plexus calcification may be a specific and relatively easily acquired biomarker for neuroinflammation and choroid plexus pathology in humans.
Assuntos
Microglia , Doenças Neuroinflamatórias , Humanos , Cálcio , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Imageamento por Ressonância Magnética , InflamaçãoRESUMO
OBJECTIVE: To confirm altered perfusion within tibial bone marrow lesions (BMLs) and improve our understanding on the relationship between BMLs and pain in knee osteoarthritis (OA). METHODS: Participants with moderate to severe knee OA were recruited and pain was assessed using the pain subscale of the Western Ontario and McMaster Universities Arthritis Index (WOMAC). Subchondral tibial BMLs were identified and graded on magnetic resonance imaging (MRI) proton density-weighted (PDW) fat suppressed images. A pharmacokinetic model was used to analyze perfusion parameters on dynamic contrast enhanced (DCE) MRI which represent transfer rates in and out of the BMLs. The relation between perfusion and pain was evaluated using multivariable linear regression after adjustment for BML grade, age, gender and body mass index (BMI). RESULTS: There were 37 participants (mean age 64.9 years, range 46-86) with radiographic Kellgren and Lawrence grades of 3 and 4 in the study knee; 75.6% had BMLs that were classified grades 1 and 2. The mean WOMAC pain score was 10.3 (0-20 scale). There was a significant correlation between BML K(el) (rate of contrast elimination) and BML grade (P = 0.001 univariate, P = 0.002 multivariate analyses), although we did not demonstrate any significant multivariate association between BML perfusion and pain. We also found an inverse relationship between pain at sleep and BML grade (P < 0.05). CONCLUSIONS: The absence of any significant association between bone perfusion and pain implies that the relationship of tibial BMLs to pain in OA is still incompletely understood. BMLs are just one component of the whole knee joint and are formed from various causes, all of which interact and collectively contribute to the genesis of pain in OA.
Assuntos
Artralgia/etiologia , Medula Óssea/patologia , Articulação do Joelho/patologia , Imageamento por Ressonância Magnética/métodos , Osteoartrite do Joelho/diagnóstico , Tíbia/patologia , Idoso , Idoso de 80 Anos ou mais , Artralgia/diagnóstico , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osteoartrite do Joelho/complicações , Projetos Piloto , Índice de Gravidade de DoençaRESUMO
OBJECTIVE: The hypothesis of this study is that changes in fluid dynamics in subchondral bone bear a functional relationship to bone remodeling and cartilage breakdown in osteoarthritis (OA). We have utilized dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) to extract kinetic parameters of bone perfusion at various stages in the development of OA in the Dunkin-Hartley guinea pig. DESIGN: Animals of four different ages (6, 9, 12 and 15 months), representing various stages in the development of OA, were studied. All animals underwent DCE MRI and perfusion data were analyzed based on the Brix two-compartment pharmacokinetic model. Regions of interest were studied at the medial and lateral tibial plateaus and compared to histological-histochemical scores of articular cartilage and subchondral bone plate thickness. RESULTS: A decrease in perfusion as well as outflow obstruction was observed in animals between 6 and 9 months of age, only in the medial tibial plateau subchondral bone. The eventual cartilage and bone lesions of OA occurred also in the medial tibia. Changes in perfusion occurred in the lateral tibia but not until OA lesions were established. Kinetic parameters of inflow were unchanged in both the medial and lateral plateaus. CONCLUSIONS: DCE MRI can be used to extract kinetic information on bone perfusion in an animal model of OA. The signal enhancement in subchondral bone temporally precedes and spatially localizes at the same site of the eventual bone and cartilage lesions. Time-intensity curves suggest outflow obstruction as an underlying mechanism.
Assuntos
Cartilagem Articular/patologia , Imageamento por Ressonância Magnética/métodos , Osteoartrite do Joelho/fisiopatologia , Tíbia/irrigação sanguínea , Fatores Etários , Animais , Artrite Experimental/fisiopatologia , Meios de Contraste , Modelos Animais de Doenças , Cobaias , Perfusão , Líquido Sinovial , Tíbia/patologiaRESUMO
BACKGROUND AND PURPOSE: Late infantile neuronal ceroid lipofuscinosis (LINCL), a form of Batten disease, is a fatal neurodegenerative genetic disorder, diagnosed via DNA testing, that affects approximately 200 children in the United States at any one time. This study was conducted to evaluate whether quantitative data derived by diffusion-weighted MR imaging (DWI) techniques can supplement clinical disability scale information to provide a quantitative estimate of neurodegeneration, as well as disease progression and severity. MATERIALS AND METHODS: This study prospectively analyzed 32 DWI examinations from 18 patients having confirmed LINCL at various stages of disease. A whole-brain apparent diffusion coefficient (ADC) histogram was fitted with a dual Gaussian function combined with a function designed to model voxels containing a partial volume fraction of brain parenchyma versus CSF. Previously published whole-brain ADC values of age-matched control subjects were compared with those of the LINCL patients. Correlations were tested between the peak ADC of the fitted histogram and patient age, disease severity, and a CNS disability scale adapted for LINCL. RESULTS: ADC values assigned to brain parenchyma were higher than published ADC values for age-matched control subjects. ADC values between patients and control subjects began to differ at 5 years of age based on 95% confidence intervals. ADC values had a nearly equal correlation with patient age (R2=0.71) and disease duration (R2=0.68), whereas the correlation with the central nervous system disability scale (R2=0.27) was much weaker. CONCLUSION: This study indicates that brain ADC values acquired using DWI may be used as an independent measure of disease severity and duration in LINCL.
Assuntos
Encéfalo/patologia , Imagem de Difusão por Ressonância Magnética/métodos , Interpretação de Imagem Assistida por Computador/métodos , Lipofuscinoses Ceroides Neuronais/diagnóstico , Índice de Gravidade de Doença , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Lipofuscinoses Ceroides Neuronais/classificação , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
Viral vector mediated gene therapy has become commonplace in clinical trials for a wide range of inherited disorders. Successful gene transfer depends on a number of factors, of which tissue tropism is among the most important. To date, definitive mapping of the spatial and temporal distribution of viral vectors in vivo has generally required postmortem examination of tissue. Here we present two methods for radiolabeling adeno-associated virus (AAV), one of the most commonly used viral vectors for gene therapy trials, and demonstrate their potential usefulness in the development of surrogate markers for vector delivery during the first week after administration. Specifically, we labeled adeno-associated virus serotype 10 expressing the coding sequences for the CLN2 gene implicated in late infantile neuronal ceroid lipofuscinosis with iodine-124. Using direct (Iodogen) and indirect (modified Bolton-Hunter) methods, we observed the vector in the murine brain for up to one week using positron emission tomography. Capsid radioiodination of viral vectors enables non-invasive, whole body, in vivo evaluation of spatial and temporal vector distribution that should inform methods for efficacious gene therapy over a broad range of applications.
Assuntos
Encéfalo/diagnóstico por imagem , Proteínas do Capsídeo/análise , Dependovirus/genética , Técnicas de Transferência de Genes , Vetores Genéticos/análise , Radioisótopos do Iodo/administração & dosagem , Cintilografia/métodos , Aminopeptidases/metabolismo , Proteínas do Capsídeo/efeitos da radiação , Dipeptidil Peptidases e Tripeptidil Peptidases/metabolismo , Terapia Genética/métodos , Humanos , Masculino , Tomografia por Emissão de Pósitrons , Serina Proteases/metabolismo , Tripeptidil-Peptidase 1 , Ureia/análogos & derivados , Ureia/farmacologiaRESUMO
BACKGROUND AND PURPOSE: Permeability surface-area product has been suggested as a marker for BBB permeability with potential applications in clinical care and research. However, few studies have demonstrated its correlation with actual quantitative measurements of BBB permeability. Our aim was to demonstrate the correlation of quantitative permeability surface-area product and BBB permeability in a murine model by histologic confirmation. MATERIALS AND METHODS: Coronal MR imaging was performed on mice treated with mannitol (n = 6) for disruption of the BBB and controls treated with saline (n = 5). Permeability surface-area product was determined by ROI placement and was compared between saline- and mannitol-treated mice. Correlation was made with contrast-enhancement measurements and immunohistologic-stained sections of tripeptidyl peptidase-1 distribution in mice treated with mannitol and saline followed by injection of a viral vector containing the CLN2 gene, which directs production of tripeptidyl peptidase-1. RESULTS: Significantly increased permeability surface-area product was seen in mannitol- compared with saline-treated mice in the whole brain (P = .008), MCA territory (P = .014), and mixed vascular territories (P = .008). These findings were compared with contrast-enhancement measurements of BBB permeability and were correlated with immunohistologic-stained sections demonstrating BBB permeability to a large vector. CONCLUSIONS: Permeability surface-area product is increased in situations with known disruptions of the BBB, as evidenced by immunologic staining of large-vector passage through the BBB and concordance with contrast-enhancement measurements in a murine model. Quantitative permeability surface-area product has potential as an imaging marker of BBB permeability.
Assuntos
Barreira Hematoencefálica/diagnóstico por imagem , Permeabilidade Capilar/fisiologia , Animais , Barreira Hematoencefálica/fisiologia , Modelos Animais de Doenças , Camundongos , Tripeptidil-Peptidase 1RESUMO
Following severe injuries that result in disorders of consciousness, recovery can occur over many months or years post-injury. While post-injury synaptogenesis, axonal sprouting and functional reorganization are known to occur, the network-level processes underlying recovery are poorly understood. Here, we test a network-level functional rerouting hypothesis in recovery of patients with disorders of consciousness following severe brain injury. This hypothesis states that the brain recovers from injury by restoring normal functional connections via alternate structural pathways that circumvent impaired white matter connections. The so-called network diffusion model, which relates an individual's structural and functional connectomes by assuming that functional activation diffuses along structural pathways, is used here to capture this functional rerouting. We jointly examined functional and structural connectomes extracted from MRIs of 12 healthy and 16 brain-injured subjects. Connectome properties were quantified via graph theoretic measures and network diffusion model parameters. While a few graph metrics showed groupwise differences, they did not correlate with patients' level of consciousness as measured by the Coma Recovery Scale - Revised. There was, however, a strong and significant partial Pearson's correlation (accounting for age and years post-injury) between level of consciousness and network diffusion model propagation time (r = 0.76, p < 0.05, corrected), i.e. the time functional activation spends traversing the structural network. We concluded that functional rerouting via alternate (and less efficient) pathways leads to increases in network diffusion model propagation time. Simulations of injury and recovery in healthy connectomes confirmed these results. This work establishes the feasibility for using the network diffusion model to capture network-level mechanisms in recovery of consciousness after severe brain injury.
Assuntos
Lesões Encefálicas/patologia , Lesões Encefálicas/fisiopatologia , Mapeamento Encefálico , Conectoma , Modelos Teóricos , Vias Neurais , Adulto , Lesões Encefálicas/diagnóstico por imagem , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Vias Neurais/diagnóstico por imagem , Vias Neurais/fisiopatologia , Oxigênio/sangue , Adulto JovemRESUMO
AIMS: We aimed to quantify the relative contributions of the medial femoral circumflex artery (MFCA) and lateral femoral circumflex artery (LFCA) to the arterial supply of the head and neck of the femur. MATERIALS AND METHODS: We acquired ten cadaveric pelvises. In each of these, one hip was randomly assigned as experimental and the other as a matched control. The MFCA and LFCA were cannulated bilaterally. The hips were designated LFCA-experimental or MFCA-experimental and underwent quantitative MRI using a 2 mm slice thickness before and after injection of MRI-contrast diluted 3:1 with saline (15 ml Gd-DTPA) into either the LFCA or MFCA. The contralateral control hips had 15 ml of contrast solution injected into the root of each artery. Next, the MFCA and LFCA were injected with a mixture of polyurethane and barium sulfate (33%) and their extra-and intra-arterial course identified by CT imaging and dissection. RESULTS: The MFCA made a greater contribution than the LFCA to the vascularity of the femoral head (MFCA 82%, LFCA 18%) and neck (MFCA 67%, LFCA 33%). However, the LFCA supplied 48% of the anteroinferior femoral neck overall. CONCLUSION: This study clearly shows that the MFCA is the major arterial supply to the femoral head and neck. Despite this, the LFCA supplies almost half the anteroinferior aspect of the femoral neck. Cite this article: Bone Joint J 2016;98-B:1582-8.
Assuntos
Artéria Femoral/anatomia & histologia , Cabeça do Fêmur/irrigação sanguínea , Colo do Fêmur/irrigação sanguínea , Adulto , Idoso , Cadáver , Meios de Contraste , Dissecação/métodos , Feminino , Artéria Femoral/diagnóstico por imagem , Cabeça do Fêmur/diagnóstico por imagem , Colo do Fêmur/diagnóstico por imagem , Gadolínio DTPA , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Distribuição Aleatória , Tomografia Computadorizada por Raios X/métodosRESUMO
BACKGROUND AND PURPOSE: Late infantile neuronal ceroid lipofuscinosis (CLN2 disease) is a uniformly fatal lysosomal storage disease resulting from mutations in the CLN2 gene. Our hypothesis was that regional analysis of cortical brain degeneration may identify brain regions that are affected earliest and most severely by the disease. MATERIALS AND METHODS: Fifty-two high-resolution 3T MR imaging datasets were prospectively acquired on 38 subjects with CLN2. A retrospective cohort of 52 disease-free children served as a control population. The FreeSurfer software suite was used for calculation of cortical thickness. RESULTS: An increased rate of global cortical thinning in CLN2 versus control subjects was the primary finding in this study. Three distinct patterns were observed across brain regions. In the first, subjects with CLN2 exhibited differing rates of cortical thinning versus age. This was true in 22 and 26 of 34 regions in the left and right hemispheres, respectively, and was also clearly discernable when considering brain lobes as a whole and Brodmann regions. The second pattern exhibited a difference in thickness from healthy controls but with no discernable change with age (9 left hemispheres, 5 right hemispheres). In the third pattern, there was no difference in either the rate of cortical thinning or the mean cortical thickness between groups (3 left hemispheres, 3 right hemispheres). CONCLUSIONS: This study demonstrates that CLN2 causes differential rates of degeneration across the brain. Anatomic and functional regions that degenerate sooner and more severely than others compared with those in healthy controls may offer targets for directed therapies. The information gained may also provide neurobiologic insights regarding the mechanisms underlying disease progression.
Assuntos
Encéfalo/patologia , Degeneração Neural/patologia , Lipofuscinoses Ceroides Neuronais/patologia , Criança , Progressão da Doença , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Estudos Retrospectivos , Tripeptidil-Peptidase 1RESUMO
Pretreatment of tumor cells with the protein kinase C (PKC) inhibitor bryostatin-1 enhances the cytotoxicity of most chemotherapeutic agents. However, in the case of paclitaxel, this effect has been shown in vitro to be best achieved when bryostatin-1 follows (rather than precedes) paclitaxel treatment. With combination trials of bryostatin-1 and paclitaxel planned for clinical trials and with only in vitro data available regarding drug sequence, we elected to undertake an in vivo study evaluating the effect of sequential bryostatin-1 and paclitaxel in a tumor-bearing mouse model and to correlate this effect to cell cycle events, tumor metabolism, and tumor blood flow. At the maximum tolerated i.p. dose, bryostatin-1 at 80 microg/kg resulted in a small but significant increase in tumor doubling time (4.2 +/- 0.3 days) compared with control tumors (3.0 +/- 0.3 days; P < 0.01). Mice treated with i.v. paclitaxel, administered at a dose of 12 mg/kg every 12 h for three doses, weekly for 3 weeks, had a tumor doubling time of 23.4 +/- 1.7 days. Mice pretreated with i.p. bryostatin-1 (80 microg/kg) followed 12 h later by i.v. paclitaxel (12 mg/kg every 12h for three doses) weekly for 3 weeks had a tumor doubling time of 9.7 +/- 1.1 days. This was significantly less (P < .001) than paclitaxel alone, which indicated an inhibitory effect by bryostatin-1 on paclitaxel therapy. In comparison, tumor-bearing mice that were treated with the same dose but with the sequence of paclitaxel followed by bryostatin-1 had a tumor doubling time of 29.6 +/- 0.6 days. This was significantly greater than the tumor doubling times for any condition tested (P < 0.01), demonstrating the sequence dependence of this combination. The efficacy of paclitaxel is dependent on mitotic entry, a step that requires activation of p34cdc2 kinase activity. Treatment with paclitaxel in vivo increased p34 cdc2 kinase activity in the mouse mammary tumors, whereas administration of bryostatin-1 before paclitaxel prevented the p34cdc2 kinase activation by paclitaxel. This was further evaluated in vitro by flow cytometry in MKN-74 human gastric cancer cells. As determined by MPM-2 labeling, which identifies cells in mitosis, pretreatment with bryostatin-1 prevented paclitaxel-treated cells from entering mitosis. Bryostatin-1 has been reported to induce changes in muscle metabolism and to decrease muscle blood flow. These events could impact on the interaction of bryostatin-1 with paclitaxel. Using proton-decoupled phosphorus nuclear magnetic resonance (31P-NMR) spectroscopy in vivo, bryostatin-1 at 80 micro1g/kg induced a decrease in both intratumoral pH and high-energy phosphates. In vivo perfusion studies, using dynamic enhanced NMR imaging with gadolinium diethylenetriamine pentaacetic acid, also demonstrated decreased tumor blood flow. These studies suggest that the inhibition of tumor response to paclitaxel by bryostatin-1 is multifactorial and includes such diverse factors as inhibition of cell entry into mitosis, a decrease in pH and energy metabolism, and a decrease in tumor blood flow. These results indicate that, as this combination enters Phase I clinical trials, the sequence of paclitaxel followed by bryostatin-1 will be critical in the clinical trial design.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Experimentais/tratamento farmacológico , Animais , Briostatinas , Proteína Quinase CDC2/efeitos dos fármacos , Proteína Quinase CDC2/metabolismo , Divisão Celular/efeitos dos fármacos , Metabolismo Energético/efeitos dos fármacos , Humanos , Concentração de Íons de Hidrogênio , Lactonas/administração & dosagem , Macrolídeos , Espectroscopia de Ressonância Magnética , Masculino , Camundongos , Camundongos Endogâmicos C3H , Mitose/efeitos dos fármacos , Neoplasias Experimentais/irrigação sanguínea , Neoplasias Experimentais/patologia , Paclitaxel/administração & dosagem , Fosfocreatina/efeitos dos fármacos , Fosfocreatina/metabolismo , Fluxo Sanguíneo Regional/efeitos dos fármacos , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologia , Células Tumorais CultivadasRESUMO
UNLABELLED: Boron neutron capture therapy (BNCT) using 4-[10B]boronophenylalanine-fructose (BPA-Fr) is in Phase II clinical trials to validate BNCT as a treatment for glioblastoma multiforme and melanoma. Successful BNCT depends on knowledge of the distribution of boron-containing agents in both tumor and normal tissue as currently determined by chemical confirmation of boron deposition in surgically removed malignant tissue before BNCT. METHODS: We used PET to noninvasively obtain in vivo information on the pharmacokinetics of the 18F-labeled analog of BPA-Fr in two patients with glioblastoma multiforme. Time-activity curves generated from the bolus injection of 18F-BPA-Fr were coinvolved to simulate a continuous infusion used for BNCT therapy. RESULTS: Distribution of 18F-BPA-Fr by PET was found to be consistent with tumor as identified by MR imaging. The 18F-BPA-Fr tumor-to-normal brain uptake ratio was 1.9 in Patient 1 and 3.1 in Patient 2 at 52 min after injection. The 18F-BPA-Fr uptake ratio in glioblastoma paralleled that of nonlabeled BPA-Fr seen in patients as previously determined by boron analysis of human glioblastoma tissue obtained from pre-BNCT surgical biopsy. CONCLUSION: Knowledge of the biodistribution of BPA-Fr enables pre-BNCT calculation of expected tissue dosimetry for a selected dose of BPA-Fr at a specific neutron exposure. Fluorine-18-BPA-Fr PET is capable of providing in vivo BPA-Fr biodistribution data that may prove valuable for patient selection and pre-BNCT treatment planning.
Assuntos
Compostos de Boro , Terapia por Captura de Nêutron de Boro , Neoplasias Encefálicas/diagnóstico por imagem , Radioisótopos de Flúor , Frutose , Glioblastoma/diagnóstico por imagem , Fenilalanina/análogos & derivados , Radiossensibilizantes , Tomografia Computadorizada de Emissão , Compostos de Boro/farmacocinética , Neoplasias Encefálicas/radioterapia , Feminino , Radioisótopos de Flúor/uso terapêutico , Frutose/farmacocinética , Glioblastoma/radioterapia , Humanos , Pessoa de Meia-Idade , Fenilalanina/farmacocinética , Radiossensibilizantes/farmacocinéticaRESUMO
BACKGROUND AND PURPOSE: LINCL is a uniformly fatal lysosomal storage disease resulting from mutations in the CLN2 gene that encodes for tripeptidyl peptidase 1, a lysosomal enzyme necessary for the degradation of products of cellular metabolism. With the goal of developing quantitative noninvasive imaging biomarkers sensitive to disease progression, we evaluated a 5-component MR imaging metric and tested its correlation with a clinically derived disease-severity score. MATERIALS AND METHODS: MR imaging parameters were measured across the brain, including quantitative measures of the ADC, FA, nuclear spin-spin relaxation times (T2), volume percentage of CSF (%CSF), and NAA/Cr ratios. Thirty MR imaging datasets were prospectively acquired from 23 subjects with LINCL (2.5-8.4 years of age; 8 male/15 female). Whole-brain histograms were created, and the mode and mean values of the histograms were used to characterize disease severity. RESULTS: Correlation of single MR imaging parameters against the clinical disease-severity scale yielded linear regressions with R2 ranging from 0.25 to 0.70. Combinations of the 5 biomarkers were evaluated by using PCA. The best combination included ADC, %CSF, and NAA/Cr (R2=0.76, P<.001). CONCLUSIONS: The multiparametric disease-severity score obtained from the combination of ADC, %CSF, and NAA/Cr whole-brain MR imaging techniques provided a robust measure of disease severity, which may be useful in clinical therapeutic trials of LINCL in which an objective assessment of therapeutic response is desired.
Assuntos
Encéfalo/patologia , Imageamento por Ressonância Magnética/métodos , Lipofuscinoses Ceroides Neuronais/patologia , Índice de Gravidade de Doença , Fatores Etários , Aminopeptidases/genética , Artefatos , Biomarcadores/metabolismo , Encéfalo/metabolismo , Criança , Pré-Escolar , Bases de Dados Factuais , Dipeptidil Peptidases e Tripeptidil Peptidases/genética , Progressão da Doença , Feminino , Humanos , Masculino , Lipofuscinoses Ceroides Neuronais/genética , Serina Proteases/genética , Tripeptidil-Peptidase 1RESUMO
OBJECTIVE: To use arterial spin labeling (ASL) to compare cerebral blood flow (CBF) patterns in minimally conscious state (MCS) patients with those in normal controls in an observational study design. METHODS: Subjects meeting MCS criteria and normal controls were identified. A pseudocontinuous ASL sequence was performed with subjects and controls in the resting awake state. Multiple CBF values for 10 predetermined regions of interest were sampled and average CBF was calculated and compared between controls and subjects. RESULTS: Ten normal controls were identified, with ages ranging from 26 to 54 years. Four subjects met the MCS criteria and received an ASL study, with one patient receiving a second study at a later date. Subjects ranged in age from 19 to 58 years and had traumatic brain injury, stroke, or hypoxic-ischemic encephalopathy. Regional CBF for controls ranged from 21.6 to 57.2 mL/100 g/min, with a pattern of relatively increased blood flow posteriorly including the posterior cingulate, parietal, and occipital cortices. CBF patterns for MCS subjects showed greater variability (from 7.7 to 33.1 mL/100 g/min), demonstrating globally decreased CBF in gray matter compared with that in normal controls, especially in the medial prefrontal and midfrontal regions. In the one subject studied longitudinally, global CBF values increased over time, which correlated with clinical improvement. CONCLUSIONS: We identified globally decreased CBF and a selective reduction of CBF within the medial prefrontal and midfrontal cortical regions as well as gray matter in MCS patients. ASL may serve as an adjunctive method to assess functional reserve in patients recovering from severe brain injuries.
Assuntos
Artérias/fisiopatologia , Córtex Cerebral/irrigação sanguínea , Circulação Cerebrovascular/fisiologia , Estado Vegetativo Persistente/fisiopatologia , Marcadores de Spin , Adulto , Mapeamento Encefálico , Feminino , Humanos , Processamento de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Observação , Oxigênio/sangue , Estado Vegetativo Persistente/metabolismo , Adulto JovemRESUMO
Measurement of bone blood flow and perfusion characteristics in a noninvasive and serial manner would be advantageous in assessing revascularization after trauma and the possible risk of avascular necrosis. Many disease states, including osteoporosis, osteoarthritis, and bone neoplasms, result in disturbed bone perfusion. A causal link between bone perfusion and remodeling has shown its importance in sustained healing and regrowth following injury. Measurement of perfusion and permeability within the bone was performed with small and macromolecular contrast media, using dynamic contrast-enhanced magnetic resonance imaging in models of osteoarthritis and the femoral head. Bone blood flow and remodeling was estimated using (18)F-Fluoride positron emission tomography in fracture healing and osteoarthritis. Multimodality assessment of bone blood flow, permeability, and remodeling by using noninvasive imaging techniques may provide information essential in monitoring subsequent rates of healing and response to treatment as well as identifying candidates for additional therapeutic or surgical interventions.
Assuntos
Osso e Ossos/irrigação sanguínea , Angiografia por Ressonância Magnética/métodos , Imagem de Perfusão/métodos , Animais , Osso e Ossos/diagnóstico por imagem , Osso e Ossos/metabolismo , Meios de Contraste/farmacocinética , Humanos , Tomografia por Emissão de Pósitrons/métodos , Radiografia , Fluxo Sanguíneo Regional/fisiologiaRESUMO
In spite of extensive accounts describing the blood supply to the femoral head, the prediction of avascular necrosis is elusive. Current opinion emphasises the contributions of the superior retinacular artery but may not explain the clinical outcome in many situations, including intramedullary nailing of the femur and resurfacing of the hip. We considered that significant additional contribution to the vascularity of the femoral head may exist. A total of 14 fresh-frozen hips were dissected and the medial circumflex femoral artery was cannulated in the femoral triangle. On the test side, this vessel was ligated, with the femoral head receiving its blood supply from the inferior vincular artery alone. Gadolinium contrast-enhanced MRI was then performed simultaneously on both control and test specimens. Polyurethane was injected, and gross dissection of the specimens was performed to confirm the extraosseous anatomy and the injection of contrast. The inferior vincular artery was found in every specimen and had a significant contribution to the vascularity of the femoral head. The head was divided into four quadrants: medial (0), superior (1), lateral (2) and inferior (3). In our study specimens the inferior vincular artery contributed a mean of 56% (25% to 90%) of blood flow in quadrant 0, 34% (14% to 80%) of quadrant 1, 37% (18% to 48%) of quadrant 2 and 68% (20% to 98%) in quadrant 3. Extensive intra-osseous anastomoses existed between the superior retinacular arteries, the inferior vincular artery and the subfoveal plexus.
Assuntos
Artéria Femoral/fisiologia , Necrose da Cabeça do Fêmur/fisiopatologia , Cabeça do Fêmur/irrigação sanguínea , Imageamento por Ressonância Magnética/métodos , Cadáver , Meios de Contraste , Artéria Femoral/anatomia & histologia , Gadolínio DTPA , Humanos , Fluxo Sanguíneo Regional/fisiologiaRESUMO
BACKGROUND AND PURPOSE: The internal carotid artery (ICA) in the rat has a single extracranial branch, which supplies the muscles of mastication. The rat ICA also has multiple intracranial branches including (from proximal to distal): multiple small perforating arteries which supply the hypothalamus and the anterior choroidal artery which supplies the choroid plexus and part of the basal ganglia. At the ICA terminus, the vessel bifurcates into the anterior and middle cerebral arteries. The purpose of this study was to demonstrate selective injection of ICA branches in the rat. MATERIALS AND METHODS: Microcatheters (mucath1 and mucath2) were fabricated by plugging the tip of 169-mum outer diameter polyimide tubing and perforating the sidewalls. A 450-mum polydimethyl-siloxane cylinder was affixed to the distal tip of mucath2 but not mucath1. We evaluated the territory of mucath1 injection ex vivo using magnetization-prepared rapid acquisition of gradient echo MR imaging of brain specimens injected at necropsy. Territories of mucath1 and mucath2 injection were evaluated in vivo with dynamic susceptibility-weighted contrast-enhanced MR imaging. The territory of mucath2 also was evaluated in vivo with fused static microPET/T1 MR images performed after [(18)F] fluorodeoxyglucose ((18)FDG) injection. We evaluated additional catheterized and injected animals at 48 hours using physical examination, T2 MR images, and postmortem brain histologic specimens. RESULTS: Gadolinium-diethylene-triamine pentaacetic acid (Gd-DTPA) and (18)FDG injected through mucath1 selectively opacified the ipsilateral cerebral hemisphere, with no contralateral opacification. Gd-DTPA injected through mucath2 selectively opacified the territories of the hypothalamic perforating arteries, and anterior choroidal artery. There was no iatrogenic complication 48 hours after 20- to 25-minute injections performed with mucath1 or mucath2. CONCLUSIONS: We have developed 2 microcatheters which can be placed in the ICA for selective injection of its branches. One microcatheter selectively injects the ipsilateral cerebral hemisphere. The other selectively injects only the hypothalamus and lateral thalamus.
Assuntos
Cateterismo/veterinária , Artérias Cerebrais , Injeções Intra-Arteriais/instrumentação , Injeções Intra-Arteriais/veterinária , Microinjeções/instrumentação , Animais , Desenho de Equipamento , Análise de Falha de Equipamento , Injeções Intra-Arteriais/métodos , Masculino , Microinjeções/métodos , Miniaturização , Ratos , Ratos Sprague-DawleyRESUMO
An important problem of the analysis of functional magnetic resonance imaging (fMRI) experiments is to achieve some noise reduction of the data without blurring the shape of the activation areas. As a novel solution to this problem, recently the propagation-separation (PS) approach has been proposed. PS is a structure adaptive smoothing method that adapts to different shapes of activation areas. In this paper, we demonstrate how this method results in a more accurate localization of brain activity. First, it is shown in numerical simulations that PS is superior over Gaussian smoothing with respect to the accurate description of the shape of activation clusters and results in less false detections. Second, in a study of 37 presurgical planning cases we found that PS and Gaussian smoothing often yield different results, and we present examples showing aspects of the superiority of PS as applied to presurgical planning.
Assuntos
Algoritmos , Mapeamento Encefálico/métodos , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/cirurgia , Imageamento Tridimensional/métodos , Imageamento por Ressonância Magnética/métodos , Reconhecimento Automatizado de Padrão/métodos , Humanos , Aumento da Imagem/métodos , Cuidados Pré-Operatórios/métodos , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
BACKGROUND: Recurrent hemarthroses in hemophilia results in synovitis and joint arthropathy. Primary prophylaxis when universally instituted at current doses can prevent joint deterioration but is expensive. Alternatively, the selective implementation of prophylaxis would require a more sensitive tool for detecting synovitis than possible with clinical surveillance or plain radiographs. Magnetic resonance imaging (MRI) is such a tool and is utilized for the evaluation of hemophilic joint disease (HJD). However, it is expensive, and requires sedation in younger children precluding its utility for monitoring of synovitis. Ultrasonography (USG) with power Doppler (USG-PDS) has been utilized to detect and quantitate synovial vascularity in other arthritides and could provide an equally effective but less costly tool for HJD, particularly in children who would not require sedation. OBJECTIVES: To determine whether USG-PDS is comparable to MRI in the evaluation of hemophilic synovitis. PATIENTS: A prospective cohort of 31 subjects including 33 joints (knees, elbows, ankles) underwent dynamic contrast enhanced (DCE)-MRI and USG-PDS. RESULTS: USG-PDS measurements of synovial thickness(r = 0.70, P < 0.0001) and synovial vascularity (r = 0.73, P < 0.0001) correlated strongly with those obtained with DCE-MRI. A cutoff of PDS intensity of 1.3 decibels (dB) per mm(2) was found to yield a sensitivity of 100% and a specificity of 94.1% in 17 joints with/without a history of hemarthroses. Pettersson radiographic scores correlated significantly with synovial thickness in adults but not children. CONCLUSIONS: Our data suggest that USG-PDS may be an inexpensive and easily implemented imaging tool for detecting hemophilic synovitis and could be useful in tailoring effective prophylaxis.