MAGNETIC RESONANCE SPECTROSCOPY AND NEUROPSYCHOLOGICAL FUNCTION

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。摘要：肾上腺脑白质营养不良是一种x连锁疾病，其基因定位于Xq28。超长链脂肪酸（VLCFA）在血浆、脑和肾上腺中积累。一种表型是大脑形式，通常在5至14岁之间导致迅速恶化和死亡。尽管血浆中VLCFA水平可用于识别异常基因型，但VLCFA水平不能识别快速进展和致命的脑型（COCALD）。骨髓移植（BMT）是治疗许多COCALD患儿的有效方法。我们已经发现，在疾病过程中相对早期的男孩移植后，BMT后的稳定性可达5年。然而，如果执行得太晚，结果将非常糟糕。因此，早期识别有生化异常的男孩的大脑疾病对阳性结果至关重要。目前的初步诊断是通过核磁共振成像和神经心理学测试来进行的，功能的迅速恶化可能已经发生；需要对这些预示着大脑疾病的变化进行敏感的早期检测。此外，脑转移后，MR成像对功能结果很敏感，需要一种反映功能变化的生物学测量方法，并告知脑转移后的大脑变化。磁共振光谱提供了满足这两种需求的可能性。我们小组使用1.5 Tesla系统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夫人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更强大的4Tesla扫描仪来测量这些脑代谢物，这将产生更精确的信息。本研究将结合MRI和神经心理学测试，检验4Tesla系统在检测神经化学谱变化方面的有效性，这些变化可能预示着大脑疾病的发生。此外，我们将检查骨髓移植前后脑代谢物的变化，以确定MRS是否比MRI或1.5 T MRS更敏感地反映神经心理测试中反映的功能变化。8岁以下的患者将使用镇静剂，8岁以上的患者将不使用镇静剂，除非他们在手术过程中被延迟或无法保持静止。

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.