Abstract
目的
功能亢进的甲状旁腺病灶需手术切除，99m锝-甲氧基异丁基异腈(99mTc-methoxyisobutylisonitrile，99mTc-MIBI)单光子发射计算机体层摄影/计算机体层摄影(single-photon emission computed tomography/computed tomography，SPECT/CT)在甲状旁腺病灶定位诊断中起重要作用，而部分结节性甲状腺肿摄取99mTc-MIBI较高，与功能亢进的甲状旁腺病灶难以鉴别。本研究旨在探讨99mTc-MIBI SPECT/CT在甲状旁腺病灶与结节性甲状腺肿鉴别诊断中的价值。
方法
回顾性分析通过99mTc-MIBI SPECT/CT拟诊为甲状旁腺病灶的68例患者，共计81个病灶。根据手术切除后病理检查结果将病灶分为甲状旁腺病灶组(69个)和结节性甲状腺肿组(12个)。测量所有病灶的放射性计数最大值(target maximum radioactivity count，Tmax)，以主动脉弓平均放射性计数作为本底放射性计数平均值(background mean radioactivity count，Bmean)，并计算二者的比值(Tmax/Bmean)，比较2组间Tmax/Bmean的差异；测量病灶CT密度最小值、平均值和最大值，比较2组间各CT密度值的差异；绘制甲状旁腺病灶患者与结节性甲状腺肿患者受试者操作特征(receiver operating characteristic，ROC)曲线，评估各CT密度值的诊断效能。
结果
甲状旁腺病灶与结节性甲状腺肿病灶99mTc-MIBI放射性摄取明显浓聚；2种病灶的CT密度值均低于正常甲状腺组织，2种病灶与甲状腺的分界均可表现为清晰或模糊2种情况。2组Tmax/Bmean值比较差异无统计学意义(P=0.221)。2组CT密度最小值、平均值及最大值比较，差异均有统计学意义(均P<0.05)。CT密度最大值的诊断效能最优，曲线下面积(area under the curve，AUC)为0.894(P<0.001)，其阈值为91 HU，敏感度为83.3%，特异度为94.2%。
结论
病灶99mTc-MIBI放射性摄取程度对甲状旁腺病灶与结节性甲状腺肿的鉴别价值有限，病灶CT密度最大值具有较高诊断效能。
Keywords: 甲状旁腺病灶, 结节性甲状腺肿, 单光子发射型计算机断层显像/计算机断层扫描, CT密度最大值
Abstract
Objective
Hyperfunctioning parathyroid lesions require surgical resection. 99mTc-methoxyisobutylisonitrile (99mTc-MIBI) single-photon emission computed tomography/computed tomography (SPECT/CT) plays an important role in the diagnosis of parathyroid lesions. Some nodular goiters have a higher uptake of 99mTc-MIBI, which is difficult to distinguish from hyperfunctioning parathyroid lesions. This study aims to explore the value of 99mTc-MIBI SPECT/CT in the differential diagnosis of parathyroid lesions and nodular goiter.
Methods
This study was a retrospective analysis. A total of 68 patients who were diagnosed as parathyroid lesions by 99mTc-MIBI SPECT/CT were enrolled, with a total of 81 lesions. According to the results of pathological examination after surgical resection, the lesions were divided into a parathyroid lesion group (n=69) and a nodular goiter group (n=12). The target maximum radioactivity count (Tmax) of all lesions was measured. The mean radioactivity count of the aortic arch was used as the background mean radioactivity count (Bmean), and the ratio of the Tmax to Bmean was calculated. The difference in Tmax/Bmean between the 2 groups was compared. The minimum, mean, and maximum of CT density in the lesion were measured. The difference of CT density between the 2 groups was compared. The receiver operating characteristic (ROC) curve of patients with parathyroid lesions and patients with nodular goiter was drawn, and the diagnostic efficacy of each CT density value was evaluated.
Results
The 99mTc-MIBI radioactive uptake in parathyroid lesions and nodular goiter lesions was significantly concentrated. The CT density values of the 2 lesions were lower than normal thyroid tissue, and the boundary between the 2 lesions and the thyroid was clear or blurred. There was no significant difference in Tmax/Bmean between the 2 groups (P=0.221). The differences in the minimum, mean and maximum of CT density between the 2 groups were statistically significant (all P<0.05). The diagnostic efficiency of maximum of CT density was the best, area under the ROC curve was 0.894 (P<0.001), the cut-off was 91 HU, the sensitivity was 83.3%, and the specificity was 94.2%.
Conclusion
The degree of 99mTc-MIBI radiation uptake in the focus has limited value in differentiating parathyroid lesions from nodular goiter, and the maximum density of CT possesses high diagnostic efficiency.
Keywords: parathyroid lesions, nodular goiter, single-photon emission computed tomography/computed tomography, maximum density of CT
原发性甲状旁腺功能亢进症是由于甲状旁腺本身病变引起的甲状旁腺激素合成与分泌过多，进一步引起钙、磷代谢紊乱的疾病，不同地区的患者临床表现不尽一致[1]。其中，单发的甲状旁腺腺瘤约占90%，其次是多发的甲状旁腺增生，而甲状旁腺癌占比不足1%[2]。手术是治疗原发性甲状旁腺功能亢进症的有效方法。在原发性甲状旁腺功能亢进症中，约90%的病灶为单发腺瘤，为减少手术并发症的发生及缩短住院时间，手术已从传统的甲状腺双侧叶探查发展为甲状腺单侧叶暴露瘤体切除[3]。改进后的手术方法对术前准确定位瘤体的要求很高。目前，常用的检查方法为甲状旁腺超声与99m锝-甲氧基异丁基异腈(99mTc-methoxyisobutylisonitrile，99mTc-MIBI)显像[4-5]。甲状旁腺99mTc-MIBI显像由平面显像发展到单光子发射计算机体层摄影/计算机体层摄影(single-photon emission computed tomography/computed tomography，SPECT/CT)断层融合显像，诊断的准确性得到了提高。由于结节性甲状腺肿的患者较多，且一些甲状旁腺腺瘤患者也常合并结节性甲状腺肿，在进行影像学检查时需鉴别甲状旁腺病灶与结节性甲状腺肿。虽然通过甲状腺超声检查可以帮助进行鉴别[6-7]，但对部分病灶的定性仍存在难度，尤其是在诊断异位病灶时，常出现漏诊。本研究基于99mTc-MIBI SPECT/CT断层融合显像，从甲状旁腺病灶99mTc-MIBI摄取程度及CT密度两个方面对甲状旁腺病灶与结节性甲状腺肿进行比较，以期为二者的鉴别诊断提供参考。
1. 对象与方法
1.1. 对象
回顾性分析2015年11月至2020年10月在中南大学湘雅医院核医学科(PET中心)通过99mTc-MIBI SPECT/CT断层融合显像拟诊为甲状旁腺病灶(腺瘤或增生)，并经手术切除后病理检查明确病灶性质的患者68例，其中男28例，女40例。68例患者共有81个病灶：54例患者为1个甲状旁腺病灶，5例为2个甲状旁腺病灶，4例为1个甲状旁腺病灶+1个结节性甲状腺肿，1例为1个甲状旁腺病灶+2个结节性甲状腺肿，3例为1个结节性甲状腺肿，1例为3个结节性甲状腺肿。共计甲状旁腺病灶69个，结节性甲状腺肿12个。
1.2. 主要药品与设备
注射用MIBI、高锝[99mTc]酸钠注射液由北京原子高科股份有限公司提供，99mTc-MIBI的放射化学纯度≥90%。SPECT/CT显像仪为荷兰飞利浦公司(Precedence 16 SPECT/CT)产品。
1.3. 方法
1.3.1. SPECT/CT图像采集
通过受试者的手背静脉或肘静脉注射99mTc-MIBI 370 MBq(10 mCi)，分别在15 min和2 h后于颈部及上胸部采集早期和延迟期图像。受检者仰卧于检查床，头向后仰，充分暴露颈部后固定头部。先采集早期和延迟期平面图像，再行颈部及上胸部CT扫描，SPECT/CT同机融合显像。CT扫描以气管为基线，CT扫描层厚为1 mm，螺距比为0.813，管电压为200 kV，管电流为280 mA。SPECT断层采集使用低能高分辨率准直器，放大倍数为1.00，采集矩阵64×64，25 s/帧，每个探头采集32帧。最后通过后处理软件得到横断面、冠状面、矢状面3个断面的CT图像及SPECT/CT同机融合图像。
1.3.2. SPECT/CT定量分析
1.3.2.1. 病灶99mTc-MIBI摄取比值的定量分析
在SPECT/CT同机融合图像上，于病灶和主动脉弓处分别勾画感兴趣区(region of interest，ROI)。在横断面上以病灶中央为中心，选择病灶中放射性摄取浓度最高的3个连续层面勾画，取各层面放射性计数最大值(target maximum radioactivity count，Tmax)，再计算3个层面Tmax的平均值(图1A)；于横断面上在主动脉弓处勾画ROI作为本底(大小为2个像素)，取其放射性计数平均值(图1B)，再对3个层面的平均值取平均值作为本底放射性计数平均值(mean background radioactivity count，Bmean)。计算横断面病灶放射性计数最大值与本底放射性计数平均值的比值(Tmax/Bmean)。
图1.
病灶及本底SPECT/CT测量方法
Figure 1 Quantitative methods for lesion and background on SPECT/CT slices
A: ROI counts of lesions measured on horizontal section; B: Reference ROI counts measured on region of aortic arch; C: CT density of lesions measured on horizontal section.
1.3.2.2. 病灶CT密度的定量分析
在CT断层图像上，于病灶处勾画ROI。在横断面上，选择病灶截面积最大的3个连续层面勾画，勾画范围控制在病灶内，取其CT密度最小值、平均值和最大值(图1C)，再对3个层面的各项测量值取平均值。以上图像分析处理均由2名核医学医师完成。
1.4. 统计学处理
运用SPSS 22.0统计学软件分析数据。计量资料采用均数±标准差( ±s)表示。对病灶的Tmax/Bmean及CT密度值进行正态分布检验；对于不符合正态分布的甲状旁腺病灶、结节性甲状腺肿病灶的Tmax/Bmean及CT密度最大值，采用Wilcoxon秩和检验进行2组间的比较；对符合正态分布的甲状旁腺病灶、结节性甲状腺肿病灶的CT密度平均值及最小值，采用独立样本t检验进行2组间的比较；采用GraphPad Prism 8软件绘制甲状旁腺病灶患者与结节性甲状腺肿患者的受试者操作特征(receiver operating characteristic，ROC)曲线，评估CT密度值的诊断效能，取约登指数最大值对应的阈值作为诊断阈值。 P<0.05表示差异有统计学意义。
2. 结 果
2.1. SPECT/CT图像
甲状旁腺病灶(腺瘤或增生)与结节性甲状腺肿病灶99mTc-MIBI放射性摄取明显浓聚；2种病灶的CT密度值均低于正常甲状腺组织，2种病灶与甲状腺的分界可表现为清晰或模糊2种情况(图2)。
图2.
病灶的代表性SPECT/CT图像
Figure 2 Representative SPECT/CT images of lesions
A: Nodular goiter is clearly demarcated from thyroid gland. B: Nodular goiter is unclearly demarcated from thyroid gland. C: Parathyroid lesion is clearly demarcated from thyroid gland. D: Parathyroid lesion is unclearly demarcated from thyroid gland.
2.2. SPECT/CT放射性摄取比值
甲状旁腺病灶组与结节性甲状腺肿组的Tmax/Bmean值分别为8.29±9.59和4.57±2.79，2组比较差异无统计学意义(组间差值95% CI：-1.86~9.29，P=0.221)。
2.3. CT密度值
甲状旁腺病灶组与结节性甲状腺肿组CT密度最小值、平均值及最大值比较，差异均有统计学意义(均P<0.05，表1)。
表1.
甲状旁腺病灶组与结节性甲状腺肿组CT密度最小值、平均值及最大值的比较
Table 1 Comparison of minimum, mean, and maximum of CT density between the parathyroid lesions group and the nodular goiter group
| 组别 | n | CT密度最大值/HU | 组间差值95% CI | P |
|---|---|---|---|---|
| 甲状旁腺病灶 | 69 | 73.46±12.25 | -47.51~-20.85 | <0.001 |
| 结节性甲状腺肿 | 12 | 107.64±20.64 |
| 组别 | CT密度平均值/HU | 组间差值95% CI | P | CT密度最小值/HU | 组间差值95% CI | P | |
|---|---|---|---|---|---|---|---|
| 甲状旁腺病灶 | 44.29±13.40 | -43.38~-13.48 | 0.001 | 13.33±16.87 | -43.47~-3.42 | 0.025 | |
| 结节性甲状腺肿 | 72.72±23.17 | 36.78±31.09 |
2.4. ROC曲线分析
甲状旁腺病灶与结节性甲状腺肿的ROC曲线(图3)分析显示：CT密度最大值的诊断效能最优，曲线下面积(area under the curve，AUC)为0.894(P<0.001)，其阈值为91 HU，敏感度为83.3%，特异度为94.2%；CT密度平均值的诊断效能次之(AUC=0.849，P<0.001)，其阈值为68.5 HU，敏感度为66.7%，特异度为98.6%；CT密度最小值的诊断效能最低(AUC=0.751，P=0.006)，其阈值为21.5 HU，敏感度为75.0%，特异度为72.5%。
图3.
甲状旁腺病灶与结节性甲状腺肿CT密度值的ROC曲线
Figure 3 ROC curve of CT density in parathyroid lesions and nodular goiter
3. 讨 论
99mTc-MIBI甲状旁腺显像是原发性甲状旁腺功能亢进患者术前的常规检查方法[8]，其对甲状旁腺病灶的精确定位为甲状旁腺微创手术提供了有效的技术支持[9-10]。相较于甲状旁腺超声检查，99mTc-MIBI甲状旁腺显像对异位的甲状旁腺病灶有更高的敏感度[8]。99mTc-MIBI甲状旁腺显像的理论基础来源于99mTc-MIBI在甲状旁腺病变组织中的清除时间明显长于正常的甲状腺组织[11]，在显像的延迟期，当正常甲状腺组织影像消退时，功能亢进的甲状旁腺组织仍显影清晰，从而达到对病变的甲状旁腺进行定位的目的。为了达到更为精确的定位，99mTc-MIBI甲状旁腺显像已由最初的平面显像发展到目前结合CT的SPECT/CT断层融合显像[12-13]，不但提供了病灶对99mTc-MIBI摄取的信息，而且提供了更精确的解剖信息，为手术的精确定位提供了依据。
然而，随着结节性甲状腺肿患者的增加，该显像方法也遇到了一定的挑战。99mTc-MIBI显像原理是MIBI与细胞线粒体膜结合，从而实现对病灶的定位[11]。在线粒体较多的正常组织或病灶组织中，99mTc-MIBI显像就会表现为放射性摄取浓聚。研究[14]发现：结节性甲状腺肿在99mTc-MIBI显像中也可表现为明显的放射性摄取浓聚，这就对甲状旁腺病灶的定性诊断造成了一定的影响。
本研究通过99mTc-MIBI SPECT/CT断层融合显像方法对甲状旁腺病灶与结节性甲状腺肿病灶进行比较。首先比较了2种病灶对99mTc-MIBI的摄取程度。为了减少因不同患者99mTc-MIBI注射剂量的差异造成的放射性计数不同的影响，本研究采用病灶Tmax与Bmean的比值作为比较依据。常规99mTc-MIBI甲状旁腺显像是将病灶放射性摄取程度与正常甲状腺放射性摄取程度进行对比，然而很多甲状腺组织的99mTc-MIBI摄取程度较高，甚至高于病灶组织，因此并不适合作为本底进行比较。研究[15]表明大血管不属于99mTc-MIBI摄取程度较高的组织，因此，本研究采取主动脉弓层面的放射性摄取程度作为本底。本研究发现2种病灶Tmax/Bmean值的差异并无统计学意义，提示仅通过病灶的放射性摄取程度进行定性诊断会出现一定的误诊。
在CT图像上，甲状旁腺病灶与结节性甲状腺肿密度均低于正常甲状腺组织[16-18]。虽然部分甲状旁腺病灶与甲状腺分界较清楚，但是也存在一些甲状旁腺病灶与甲状腺组织分界不清，尤其是甲状腺腺内型的甲状旁腺病灶[19-20]。因此，无论是从密度还是从与甲状腺的关系上进行鉴别均存在一定的困难。
本研究进一步从CT密度值的角度对病灶进行比较。为了减少病灶内钙化、囊变对CT密度值评估的影响，选取无明显钙化或囊变的层面进行病灶CT密度值的测量。本研究发现：甲状旁腺病灶的CT密度最小值、平均值和最大值低于结节性甲状腺肿。采用ROC曲线分析评估CT密度值对病灶定性诊断的价值，结果发现：CT密度最大值的诊断效能最优，其阈值为91 HU，敏感度为83.3%，特异度为94.2%。
本研究不足之处在于通过99mTc-MIBI断层融合显像被诊断为甲状旁腺病灶，再经手术切除后病理检查证实为结节性甲状腺肿的病例数较少，其主要原因是在本单位通过99mTc-MIBI断层融合显像被误诊为甲状旁腺病灶的结节性甲状腺肿病例较少。
综上，病灶99mTc-MIBI放射性摄取程度对甲状旁腺病灶与结节性甲状腺肿的鉴别价值有限，病灶CT密度最大值对甲状旁腺病灶与结节性甲状腺肿鉴别诊断具有一定的价值。
利益冲突声明
作者声称无任何利益冲突。
原文网址
http://xbyxb.csu.edu.cn/xbwk/fileup/PDF/2021091018.pdf
参考文献
- 1. Meng L, Liu S, Al-Dayyeni A, et al. Comparison of initial clinical presentations between primary hyperparathyroidism patients from New Brunswick and Changsha[J]. Int J Endocrinol, 2018: 6282687. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2. Koberstein W, Fung C, Romaniuk K, et al. Accuracy of dual phase single-photon emission computed tomography/computed tomography in primary hyperparathyroidism: correlation with serum parathyroid hormone levels[J]. Can Assoc Radiol J, 2016, 67(2): 115-121. [DOI] [PubMed] [Google Scholar]
- 3. Russell CF, Laird JD, Ferguson WR. Scan-directed unilateral cervical exploration for parathyroid adenoma: a legitimate approach? [J]. World J Surg, 1990, 14(3): 406-409. [DOI] [PubMed] [Google Scholar]
- 4. Lumachi F, Ermani M, Basso S, et al. Localization of parathyroid tumours in the minimally invasive era: which technique should be chosen? Population-based analysis of 253 patients undergoing parathyroidectomy and factors affecting parathyroid gland detection[J]. Endocr Relat Cancer, 2001, 8(1): 63-69. [DOI] [PubMed] [Google Scholar]
- 5. Mohamed SE, Li X, Khadra H, et al. Different surgical approaches in parathyroid adenoma resections[J]. Gland Surg, 2013, 2(4): 227-229. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6. Mariani G, Gulec SA, Rubello D, et al. Preoperative localization and radioguided parathyroid surgery[J]. J Nucl Med, 2003, 44(9): 1443-1458. [PubMed] [Google Scholar]
- 7. Wang Z, Fu B, Xiao Y, et al. Primary thyroid lymphoma has different sonographic and color Doppler features compared to nodular goiter[J]. J Ultrasound Med, 2015, 34(2): 317-323. [DOI] [PubMed] [Google Scholar]
- 8. Liddy S, Worsley D, Torreggiani W, et al. Preoperative imaging in primary hyperparathyroidism: Literature review and recommendations[J]. Can Assoc Radiol J, 2017, 68(1): 47-55. [DOI] [PubMed] [Google Scholar]
- 9. Mariani G, Gulec SA, Rubello D, et al. Preoperative localization and radioguided parathyroid surgery[J]. J Nucl Med, 2003, 44(9): 1443-1458. [PubMed] [Google Scholar]
- 10. Moure D, Larrañaga E, Domínguez-Gadea L, et al. 99mTc-sestamibi as sole technique in selection of primary hyperparathyroidism patients for unilateral neck exploration[J]. Surgery, 2008, 144(3): 454-459. [DOI] [PubMed] [Google Scholar]
- 11. Mehta NY, Ruda JM, Kapadia S, et al. Relationship of technetium Tc 99m sestamibi scans to histopathological features of hyperfunctioning parathyroid tissue[J]. Arch Otolaryngol Head Neck Surg, 2005, 131(6): 493-498. [DOI] [PubMed] [Google Scholar]
- 12. Wong KK, Fig LM, Gross MD, et al. Parathyroid adenoma localization with 99mTc-sestamibi SPECT/CT: A meta-analysis[J]. Nucl Med Commun, 2015, 36(4): 363-375. [DOI] [PubMed] [Google Scholar]
- 13. 赵敏, 李新辉, 黄金, 等. SPECT/CT在甲状旁腺功能亢进中的诊断价值及其与多种影像学方法的比较[J]. 中南大学学报(医学版), 2015, 40(9): 1016-1022. [DOI] [PubMed] [Google Scholar]; ZHAO Min, LI Xinhui, HUANG Jin, et al. Value of single photon emission computed tomography/computerized tomography in the diagnosis of hyperparathyroidism and the comparative study with multiple imaging modality[J]. Journal of Central South University. Medical Science, 2015, 40(9): 1016-1022. [DOI] [PubMed] [Google Scholar]
- 14. Palestro CJ, Tomas MB, Tronco GG. Radionuclide imaging of the parathyroid glands[J]. Semin Nucl Med, 2005, 35(4): 266-276. [DOI] [PubMed] [Google Scholar]
- 15. Sutter CW, Joshi MJ, Stadalnik RC. Noncardiac uptake of technetium-99m MIBI[J]. Semin Nucl Med, 1994, 24(1): 84-86. [DOI] [PubMed] [Google Scholar]
- 16. Youserm DM, Huang T, Loevner LA, et al. Clinical and economic impact of incidental thyroid lesions found with CT and MR[J]. AJNR Am J Neuroradiol, 1997, 18(8): 1423-1428. [PMC free article] [PubMed] [Google Scholar]
- 17. Hoang JK, Sung WK, Bahl M, et al. How to perform parathyroid 4D CT: tips and traps for technique and interpretation[J]. Radiology, 2014, 270(1): 15-24. [DOI] [PubMed] [Google Scholar]
- 18. 胡娜, 肖立志, 吴永港, 等. 原发性甲状旁腺功能亢进症PET-CT表现Ⅰ例[J]. 中南大学学报(医学版), 2015, 40(6): 697-701. [DOI] [PubMed] [Google Scholar]; HU Na, XIAO Lizhi, WU Yonggang, et al. A case of PET-CT imaging for primary hyperparathyroidism[J]. Journal of Central South University. Medical Science, 2015, 40(6): 697-701. [DOI] [PubMed] [Google Scholar]
- 19. Chen J, Ma Z, Yu J. Diagnostic pitfalls in a cystic ectopic intrathyroidal parathyroid adenoma mimicking a nodular goiter: A care-compliant case report[J]. Medicine (Baltimore), 2019, 98(5): e14351. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 20. Kaushal DK, Mishra A, Mittal N, et al. Successful removal of intrathyroidal parathyroid adenoma diagnosed and accurately located preoperatively by parathyroid scintigraphy (SPECT-CT) [J]. Indian J Nucl Med, 2010, 25(2): 62-63. [DOI] [PMC free article] [PubMed] [Google Scholar]