ASSESSMENT OF ADRENOLEUKODYSTROPHY LESIONS BY HIGH FIELD MRS IN NON-SEDATED PED

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 背景：早期发现儿童起病的脑肾上腺脑白质营养不良(ALD)白质病变非常重要，因为造血细胞移植(HCT)是目前唯一有效的治疗方法，只有在病程早期进行才是有益的。 目的：建立反映ALD患者脑部疾病进展的可靠生化标志物，为制定治疗方案提供依据。 方法：采用质子磁共振波谱(MRS)结合LC模型分析方法，对17例未服用镇静剂的患者和26例健康志愿者(成人21例，年龄匹配的5例)在4T下枕叶、额叶白质和穹隆压部的脑代谢产物进行定量。 结果：可靠地测定了12种代谢物的绝对浓度，其中7种被确定为病变发展的标志。其中，含肌酸和胆碱的化合物是最弱的标志物，而N-乙酰天冬氨酸、谷氨酰胺和脂类+乳酸是最强的标志物。标记物的大范围变化使得在常规MRI检测异常之前能够检测到病变形成的早期神经化学变化。许多代谢物的浓度在患者和对照组的正常白质之间也有显着差异，表明在没有脑部疾病的情况下，生化变化。对6名患者进行了HCT后神经化学改善的测量。 结论：在不需要镇静的情况下，使用高场1H磁共振波谱可以高精度地评估肾上腺脑白质营养不良的进展及其治疗效果。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Background: Early detection of white matter lesions in childhood-onset cerebral adrenoleukodystrophy (ALD) is important as hematopoietic cell transplantation (HCT), currently the only effective treatment, is beneficial only if performed early in the disease course. Objective: To establish reliable biochemical markers of cerebral disease progression in patients with ALD to aid in treatment planning. Methods: The authors used proton magnetic resonance spectroscopy (MRS) in combination with LCModel analysis to quantify brain metabolites in small volumes (3 to 16 mL) in the occipital and frontal white matter and the splenium of the corpus callosum of 17 unsedated patients and 26 healthy volunteers (adult n = 21, age-matched n = 5) at 4 tesla. Results: Absolute concentrations of 12 metabolites were reliably determined, seven of which were established as markers of lesion development. Among these, creatine and choline containing compounds were the weakest markers while N-acetylaspartate, glutamine, and lipids + lactate were the strongest. The large extent of changes in the markers enabled detection of early neurochemical changes in lesion formation prior to detection of abnormalities by conventional MRI. Concentrations of a number of metabolites were also significantly different between normal appearing white matter of patients and controls indicating biochemical alterations in the absence of cerebral disease. Neurochemical improvements following HCT were measured in six patients. Conclusions: The progression of adrenoleukodystrophy, as well as effectiveness of its treatment, can be assessed with high precision using high field 1H magnetic resonance spectroscopy in individual patients without the need for sedation.