磁共振波谱分析在遗传性平滑肌瘤病和肾细胞癌综合征中检测延胡索酸水合酶缺陷

MR Spectroscopy for Detecting Fumarate Hydratase Deficiency in Hereditary Leiomyomatosis and Renal Cell Carcinoma Syndrome.

机构信息

From the Departments of Radiology (G.W., G.L., S.P., Y.L., J.X.) and Urology (J.W., Y.X., W.K., W.X., J.Z.), Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Pujian Rd, 200127 Shanghai, China; and Clinical & Technical Solutions, Philips Healthcare, Beijing, China (P.S.).

出版信息

Radiology. 2022 Dec;305(3):631-639. doi: 10.1148/radiol.212984. Epub 2022 Aug 9.

DOI:10.1148/radiol.212984

PMID:35943337

Abstract

Background Noninvasive in vivo detection of fumarate accumulation may help identify fumarate hydratase deficiency in renal cancer related to hereditary leiomyomatosis and renal cell carcinoma (HLRCC) syndrome. Purpose To investigate the feasibility of MR spectroscopy (MRS) in detecting elevated fumarate levels in HLRCC-associated renal cancers. Materials and Methods This study included an experimental xenograft mouse model and prospective clinical cohort. First, MRS was performed on patient-derived tumor xenograft models and control models to detect fumarate. Then, consecutive participants with clinical suspicion of HLRCC-associated renal tumors were enrolled. For the detection of fumarate, MRS results were classified as detected, borderline, undetected, or technical failure. The sensitivity, specificity, and accuracy of MRS for diagnosing HLRCC-associated renal cancer were assessed. The signal-to-noise ratio (SNR) of the fumarate peak was calculated and evaluated with receiver operating characteristic curve analysis. Results Fumarate peaks were detected at 6.54 parts per million in all three patient-derived xenograft models. A total of 38 participants (21 men; mean age, 47 years [range, 18-71 years]) with 46 lesions were analyzed. All primary HLRCC-associated renal cancers showed a fumarate peak; among the seven metastatic HLRCC-associated lesions, a fumarate peak was detected in three lesions and borderline in two. When only detected peaks were regarded as positive findings, the sensitivity, specificity, and accuracy of MRS at the lesion level were 69% (nine of 13 lesions), 100% (33 of 33 lesions), and 91% (42 of 46 lesions), respectively. When borderline peaks were also included as a positive finding, the sensitivity, specificity, and accuracy reached 85% (11 of 13 lesions), 88% (29 of 33 lesions), and 87% (40 of 46 lesions), respectively. The SNR of fumarate showed an area under the receiver operating characteristic curve of 0.87 for classifying HLRCC-associated tumors. Conclusion MR spectroscopy of fumarate was sensitive and specific for hereditary leiomyomatosis and renal cell carcinoma-associated tumors. © RSNA, 2022

摘要

背景

非侵入性体内检测富马酸积累可能有助于识别与遗传性平滑肌瘤病和肾细胞癌（HLRCC）综合征相关的肾细胞癌中的富马酸hydratase 缺乏症。

目的

探讨磁共振波谱（MRS）检测 HLRCC 相关肾癌中富马酸水平升高的可行性。

材料与方法

本研究包括实验性异种移植小鼠模型和前瞻性临床队列。首先，对患者来源的肿瘤异种移植模型和对照模型进行 MRS 检测以检测富马酸。然后，连续招募临床怀疑为 HLRCC 相关肾肿瘤的患者。对于富马酸的检测，MRS 结果分为检测、边界、未检测或技术失败。评估 MRS 诊断 HLRCC 相关肾癌的灵敏度、特异性和准确性。计算富马酸峰的信噪比（SNR），并通过接收者操作特征曲线分析进行评估。

结果

在所有三个患者来源的异种移植模型中均检测到 6.54ppm 的富马酸峰。共分析了 38 名患者（21 名男性；平均年龄 47 岁[范围 18-71 岁]）和 46 个病灶。所有原发性 HLRCC 相关肾癌均显示富马酸峰；在 7 个转移性 HLRCC 相关病变中，有 3 个病变和 2 个边界病变检测到富马酸峰。当仅将检测到的峰值视为阳性发现时，MRS 在病变水平的灵敏度、特异性和准确性分别为 69%（13 个病变中的 9 个）、100%（33 个病变中的 33 个）和 91%（46 个病变中的 42 个）。当也将边界峰包含为阳性发现时，灵敏度、特异性和准确性分别达到 85%（13 个病变中的 11 个）、88%（33 个病变中的 29 个）和 87%（46 个病变中的 40 个）。富马酸的 SNR 显示用于分类 HLRCC 相关肿瘤的接收器操作特征曲线下面积为 0.87。