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

这个子项目是许多利用 由NIH/NCRR资助的中心赠款提供的资源。子项目及 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 背景资料：早期发现儿童期脑肾上腺脑白质营养不良（ALD）的白色病变是重要的，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有益。 目的：建立可靠的生化指标，以帮助治疗计划的ALD患者的脑疾病进展。 研究方法：作者使用质子磁共振波谱（MRS）结合LC模型分析，在4特斯拉下定量17名未镇静患者和26名健康志愿者（成人n = 21，年龄匹配n = 5）的枕骨和额叶白色物质以及胼胝体压部中小体积（3至16 mL）的脑代谢物。 结果：12种代谢物的绝对浓度被可靠地确定，其中7种被确定为病变发展的标志物。其中，肌酸和胆碱含化合物是最弱的标志物，而N-乙酰天冬氨酸，谷氨酰胺，脂质+乳酸是最强的。标记物的大范围变化使得能够在通过常规MRI检测异常之前检测病变形成中的早期神经化学变化。许多代谢物的浓度在患者和对照组正常出现的白色物质之间也存在显著差异，表明在没有脑疾病的情况下存在生化改变。在6名患者中测量了HCT后的神经化学改善。 结论：肾上腺脑白质营养不良的进展，以及其治疗的有效性，可以使用高场1H磁共振波谱在个体患者中进行高精度评估，而无需镇静。

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.