MAGNETIC RESONANCE SPECTROSCOPY AND NEUROPSYCHOLOGICAL FUNCTION

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。摘要：肾上腺脑白质营养不良是一种X连锁疾病，基因定位于Xq28。超长链脂肪酸(VLCFA)在血浆、大脑和肾上腺中积累。一种表型是导致快速恶化和死亡的脑型，通常在5岁到14岁之间。尽管血浆VLCFA水平可用于识别异常基因，但VLCFA水平不能识别快速进展和致命的脑型(COCALD)。骨髓移植(BMT)对许多患有COCALD的儿童是有效的。我们发现，在疾病病程相对较早的时候移植的男孩，在骨髓移植后长达五年的时间里是稳定的。然而，如果实施得太晚，结果会非常糟糕。因此，在生化异常的男孩中及早识别脑部疾病对于积极的结果是至关重要的。目前通过磁共振成像结合神经心理测试进行初步诊断，可能已经发生了功能的迅速恶化；对这种变化的敏感早期检测，需要先兆脑部疾病。此外，骨髓移植后，MR成像对功能结果很敏感，需要一种生物学方法来反映骨髓移植后的功能变化并告知大脑变化。光谱学提供了同时满足这两种需求的可能性。我们小组使用1.5特斯拉系统和其他小组的初步证据表明，MRS对与ALD相关的异常很敏感。这些发现表明，COCALD夫人的早期识别和灵敏的治疗后监测具有巨大的潜力。在这项研究中，我们有机会使用功能更强大的4Tesla扫描仪来测量这些大脑代谢物，从而获得更准确的信息。这项研究将结合核磁共振成像和神经心理测试来检验4Tesla系统在检测可能预示脑部疾病发病的神经化学特征变化方面的有效性。此外，我们将检查骨髓移植前后大脑代谢物的变化，以确定MRS是否比MRI或1.5T MRS更敏感地反映神经心理测试中反映的功能变化；研究中选定的患者将在CMRR的4特斯拉磁体中进行扫描。8岁以下的患者将被镇静，而8岁以上的患者将不会被镇静，除非他们在手术过程中被延迟并无法保持静止。

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. Summary: Adrenoleukodystrophy is an X-linked disorder with the gene localized to Xq28. Very-long-chain fatty acids (VLCFA) accumulate in plasma, brain, and adrenal glands. One phenotype is a cerebral form which results in rapid deterioration and death, usually between ages 5 and 14. Although VLCFA levels in plasma serve to identify abnormal genotype, VLCFA levels cannot identify the rapidly progressive and fatal cerebral form (COCALD). Bone marrow transplantation (BMT) has been effective for many children with COCALD. We have found stability after BMT for up to five years for boys transplanted relatively early in the course of the disease. However, if performed too late, the outcomes are very poor. Thus, early identification of cerebral disease in boys with the biochemical abnormality is critical for positive outcome. Initial diagnosis is currently made with MR imaging together with neuropsychological testing, a rapid deterioration of function can have already occurred; sensitive early detection of such changes that herald cerebral disease is needed. Furthermore, after BMT, MR imaging has been sensitive to functional outcomes, a biological measure is needed that reflects functional change and informs about cerebral changes after BMT. MR spectroscopy offers the possibility of meeting both those needs. Preliminary evidence from our group using the 1.5 Tesla system and other groups indicate that MRS is sensitive to abnormalities associated with ALD. Such findings suggest the enormous potential for early identification and sensitive post-treatment monitoring of COCALD MRS. We have the opportunity to measure these brain metabolites using the more powerful 4Tesla scanner in this research that will yield more precise information. This study will examine the effectiveness of the 4Tesla system in detecting changes in neurochemical profile that may herald the onset of cerebral disease in conjunction with MRI and neuropsychological testing. In addition, we will examine changes in cerebral metabolites before and after bone marrow transplantation to determine whether MRS will more sensitively reflect functional changes as reflected on neuropsychological testing than does MRI or 1.5 T MRS> Patients selected in the study will be scanned in the 4 Tesla magnet at the CMRR. Patients under 8 will be sedated and those over 8 will not be sedated unless they are delayed and unable to stay still during the procedure.