MAGNETIC RESONANCE SPECTROSCOPY AND NEUROPSYCHOLOGICAL FUNCTION

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。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Xq 28。极长链脂肪酸（VLCFA）在血浆、脑和肾上腺中蓄积。一种表型是大脑型，其导致快速恶化和死亡，通常在5至14岁之间。尽管血浆中的VLCFA水平用于识别异常基因型，但VLCFA水平不能识别快速进行性和致死性脑型（COCALD）。 骨髓移植（BMT）对许多COCALD儿童有效。我们已经发现，在疾病过程中相对较早移植的男孩在BMT后长达五年的稳定性。但是，如果进行得太晚，结果非常糟糕。因此，早期发现脑疾病的男孩与生化异常是至关重要的积极成果。目前的初步诊断是通过磁共振成像和神经心理学测试进行的，功能的快速恶化可能已经发生;需要对这种预示大脑疾病的变化进行敏感的早期检测。 此外，在BMT后，MR成像对功能结果敏感，需要一种生物学测量来反映BMT后的功能变化并告知大脑变化。 磁共振波谱提供了满足这两种需求的可能性。我们使用1.5特斯拉系统的小组和其他小组的初步证据表明，MRS对ALD相关的异常敏感。这些发现表明，COCALD MRS的早期识别和敏感的治疗后监测具有巨大的潜力。我们有机会在本研究中使用功能更强大的4 Tesla扫描仪测量这些大脑代谢物，这将产生更精确的信息。 这项研究将检查4 Tesla系统在检测神经化学特征变化方面的有效性，这些变化可能预示着与MRI和神经心理学测试相结合的脑部疾病的发作。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1.5 T MRS更敏感地反映神经心理学测试所反映的功能变化。研究中选择的患者将在4特斯拉磁体中以CMRR进行扫描。8岁以下的患者将被镇静，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且无法保持静止。

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.