RESUMEN
Objective: To promote advanced research using magnetic resonance imaging (MRI) in the diagnosis of and screening for osteoporosis by looking for correlations among the T-scores measured by dual-energy X-ray absorptiometry (DEXA), the apparent diffusion coefficient (ADC) values on diffusion-weighted imaging (DWI), and the T1-weighted signal intensity values. Materials and Methods: This was a prospective study of postmenopausal women with no contraindications to MRI and no history of cancer who underwent DEXA within 30 days before or after the MRI examination. A 3.0-T scanner was used in order to acquire sagittal sequences targeting the lumbar spine. Results: Thirteen women underwent DEXA and MRI. In two cases, the MRI was discontinued early. Therefore, the final sample comprised 11 patients. The ADC values and T1-weighted signal intensity were found to be higher in patients with osteoporosis. However, among the patients > 60 years of age with osteoporosis, ADC values were lower and T1-weighted signal intensity was even higher. Conclusion: It is unlikely that MRI will soon replace DEXA for the diagnostic workup of osteoporosis. Although DWI and ADC mapping are useful for understanding the pathophysiology of osteoporosis, we believe that T1-weighted sequences are more sensitive than is DWI as a means of performing a qualitative analysis of vertebral alterations.
Objetivo: Promover pesquisas avançadas usando ressonância magnética (RM) no diagnóstico e rastreamento de osteoporose, procurando correlações entre os escores T medidos por absorciometria de raios-X de dupla energia (DEXA), valores de coeficiente de difusão aparente (ADC) na difusão e valores de intensidade de sinal ponderado em T1. Materiais e Métodos: Estudo prospectivo de mulheres na pós-menopausa sem contraindicações para RM e sem histórico de câncer que foram submetidas a DEXA 30 dias antes ou após o exame de RM. Um scanner 3.0-T foi utilizado para adquirir sequências sagitais direcionadas à coluna lombar. Resultados: Treze mulheres foram submetidas a DEXA e RM. Em dois casos, a RM foi interrompida precocemente. Portanto, a amostra final foi composta por 11 pacientes. Os valores de ADC e intensidade de sinal ponderado em T1 foram mais elevados nas pacientes com osteoporose. No entanto, no subgrupo de pacientes > 60 anos de idade com osteoporose, os valores de ADC foram menores e a intensidade do sinal ponderado em T1 foi ainda maior. Conclusão: É improvável que a RM substitua DEXA para a investigação diagnóstica da osteoporose no futuro próximo. Embora a difusão e o mapeamento ADC sejam úteis para a compreensão da fisiopatologia da osteoporose, acreditamos que as sequências ponderadas em T1 são mais sensíveis do que a difusão como meio de realizar uma análise qualitativa das alterações vertebrais.
RESUMEN
Abstract Objective: To promote advanced research using magnetic resonance imaging (MRI) in the diagnosis of and screening for osteoporosis by looking for correlations among the T-scores measured by dual-energy X-ray absorptiometry (DEXA), the apparent diffusion coefficient (ADC) values on diffusion-weighted imaging (DWI), and the T1-weighted signal intensity values. Materials and Methods: This was a prospective study of postmenopausal women with no contraindications to MRI and no history of cancer who underwent DEXA within 30 days before or after the MRI examination. A 3.0-T scanner was used in order to acquire sagittal sequences targeting the lumbar spine. Results: Thirteen women underwent DEXA and MRI. In two cases, the MRI was discontinued early. Therefore, the final sample comprised 11 patients. The ADC values and T1-weighted signal intensity were found to be higher in patients with osteoporosis. However, among the patients > 60 years of age with osteoporosis, ADC values were lower and T1-weighted signal intensity was even higher. Conclusion: It is unlikely that MRI will soon replace DEXA for the diagnostic workup of osteoporosis. Although DWI and ADC mapping are useful for understanding the pathophysiology of osteoporosis, we believe that T1-weighted sequences are more sensitive than is DWI as a means of performing a qualitative analysis of vertebral alterations.
Resumo Objetivo: Promover pesquisas avançadas usando ressonância magnética (RM) no diagnóstico e rastreamento de osteoporose, procurando correlações entre os escores T medidos por absorciometria de raios-X de dupla energia (DEXA), valores de coeficiente de difusão aparente (ADC) na difusão e valores de intensidade de sinal ponderado em T1. Materiais e Métodos: Estudo prospectivo de mulheres na pós-menopausa sem contraindicações para RM e sem histórico de câncer que foram submetidas a DEXA 30 dias antes ou após o exame de RM. Um scanner 3.0-T foi utilizado para adquirir sequências sagitais direcionadas à coluna lombar. Resultados: Treze mulheres foram submetidas a DEXA e RM. Em dois casos, a RM foi interrompida precocemente. Portanto, a amostra final foi composta por 11 pacientes. Os valores de ADC e intensidade de sinal ponderado em T1 foram mais elevados nas pacientes com osteoporose. No entanto, no subgrupo de pacientes > 60 anos de idade com osteoporose, os valores de ADC foram menores e a intensidade do sinal ponderado em T1 foi ainda maior. Conclusão: É improvável que a RM substitua DEXA para a investigação diagnóstica da osteoporose no futuro próximo. Embora a difusão e o mapeamento ADC sejam úteis para a compreensão da fisiopatologia da osteoporose, acreditamos que as sequências ponderadas em T1 são mais sensíveis do que a difusão como meio de realizar uma análise qualitativa das alterações vertebrais.
RESUMEN
The crosstalk between hematopoietic stem/progenitor cells (HSC), both normal and leukemic, and their neighboring bone marrow (BM) microenvironment (niche) creates a reciprocal dependency, a master regulator of biological process, and chemotherapy resistance. In acute myeloid leukemia (AML), leukemic stem/progenitor cells (LSC) anchored in the protective BM microenvironment, reprogram and transform this niche into a leukemia-supporting and chemoprotective environment. One most important player involved in this crosstalk are CXCL12, produced by the BM mesenchymal stromal cells, and its receptor CXCR4, present onto HSC. The downstream molecular mechanisms involved in CXCL12/CXCR4 axis have many targets, including the Src family members of non-receptor tyrosine kinase (SFK). We herein study the role of one SFK member, the Hematopoietic Cell Kinase (HCK), in CXCL12/CXCR4 pathway and its contribution to the AML pathogenesis. We verified that the inhibition of HCK severely impaired CXCL12-induced migration of leukemic cell lines and CD34 positive cells from AML patients bone marrow, through a disruption of the activation of CXCL12/CXCR4/PI3K/AKT and CXCL12/CXCR4/MAPK/ERK signaling, and by a decreased cytoskeleton dynamic through a lower rate of actin polymerization. We provide new insights into the key role of HCK in conferring a migratory advantage to leukemic cells thought CXCL12/CXCR4 axis. HCK represents an important protein of the main pathway involved in the crosstalk between HSC, and their surrounding milieu. Thus, HCK inhibition could represent a novel approach for the treatment of the acute myeloid leukemia.