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临床研究
采用磁共振2D-MRCP电影成像无创评估胰腺外分泌功能的可行性研究
吴巧玲 王沄 孙照勇 胡格丽 王一鸣 金征宇 薛华丹

WU Q L, WANG Y, SUN Z Y, et al. Noninvasively evaluate pancreatic exocrine function using 2D cine-dynamic MRCP under physiological conditions: A preliminary study[J]. Chin J Magn Reson Imaging, 2023, 14(9): 81-85.引用本文:吴巧玲, 王沄, 孙照勇, 等. 采用磁共振2D-MRCP电影成像无创评估胰腺外分泌功能的可行性研究[J]. 磁共振成像, 2023, 14(9): 81-85. DOI:10.12015/issn.1674-8034.2023.09.014.


[摘要] 目的 探讨采用二维磁共振胰胆管成像(two-dimensional magnetic resonance cholangiopancreatography, 2D-MRCP)动态电影成像序列定量检测健康志愿者摄入脂餐后主胰管内生理胰液分泌变化的可行性。材料与方法 招募健康志愿者36人,所有志愿者均行2D-MRCP电影序列扫描,每个电影序列选择胰头层面,在胰头位置施加宽度为20 mm的空间选择反转脉冲(inversion pulse, IR)饱和带,单层屏气扫描,屏气时长为5 s,屏气间隔为15 s,脂餐前屏气20次采集并测量该志愿者胰液分泌的频率和长度(基础状态的频率和长度),脂餐后屏气60次,观察脂餐后胰液分泌的动态变化。采用配对t检验比较脂餐前后胰液分泌长度的变化,并比较脂餐后胰液分泌频率较基础频率增加百分比。根据年龄将志愿者分为三组,第一组年龄≤30岁,第二组年龄>30岁并≤60岁,第三组年龄>60岁,采用Kruskal-Wallis法比较脂餐后胰液分泌平均频率、平均长度与年龄之间的关系。结果 脂餐前胰液分泌的频率为21.32%±1.20%,脂餐后胰液分泌的频率为29.82%±1.11%,频率增加了8.50%,差异具有统计学意义(P<0.001);脂餐前胰液分泌的长度为(11.06±7.27)mm,脂餐后胰液分泌的长度为(15.34±4.61)mm,长度平均增加了4.28 mm,差异具有统计学意义(P<0.05)。第一组与第二、三组之间胰液平均频率和长度差异均具有统计学意义(P<0.001);第二组与第三组之间胰液平均频率和长度差异均无统计学意义(P=0.477,P=0.316)。结论 2D-MRCP动态电影序列可定量检测脂餐后胰液分泌流量变化,该序列对无创评估生理状态下胰腺外分泌功能具有临床价值。脂餐后胰液分泌功能随着年龄的增长可能呈下降趋势。
[Abstract] Objective To explore the feasibility of using two-dimensional magnetic resonance cholangiopancreatography (2D-MRCP) dynamic cine imaging sequence to quantitatively detect changes in physiological pancreatic juice secretion in the main pancreatic duct of healthy volunteers after consuming a fat meal.Materials and Methods Thirty-six healthy volunteers were recruited, all of whom underwent 2D-MRCP film sequence scanning. Each movie sequence selects the pancreatic head layer and applies a 20 mm wide spatial selection inversion pulse (IR) saturation band at the pancreatic head position. Single layer breath-holding scan, with a breath-holding duration of 5 s and a breath-holding interval of 15 s. Collect and measure the frequency and length of pancreatic juice secretion (basic state frequency and length) of the volunteer 20 times before the fat meal, and hold the breath 60 times after the fat meal to observe the dynamic changes in pancreatic juice secretion after the fat meal. Compare the changes in pancreatic secretion length before and after a fat meal using paired t-tests, and compare the percentage increase in pancreatic secretion frequency after a fat meal compared to the base frequency. Volunteers were divided into three groups based on age. The first group was ≤ 30 years old, the second group was > 30 years old and ≤ 60 years old, and the third group was > 60 years old. The Kruskal Wallis method was used to compare the average frequency of pancreatic juice secretion after a fat meal, and the relationship between the average length and age.Results The frequency of pancreatic juice secretion before fat meal was 21.32%±1.20%, and the frequency of pancreatic juice secretion after fat meal was 29.82%±1.11%, an increase of 8.50%, with a statistical difference of P<0.001. The length of pancreatic juice secretion before the fat meal was (11.06±7.27) mm, and the length of pancreatic juice secretion after the fat meal was (15.34±4.61) mm, with an average increase of 4.28 mm, showing a statistical difference of P=0.004. According to age group, there were statistical differences in the average frequency and length of pancreatic juice between the first group and the second and third groups, P<0.001; There was no statistically significant difference in the average frequency and length of pancreatic juice between the second and third groups, with P-values of 0.477 and 0.316, respectively.Conclusions The 2D-MRCP dynamic movie sequence can quantitatively detect changes in pancreatic juice secretion flow after a fat meal, and this sequence has clinical value for non-invasive evaluation of pancreatic exocrine function under physiological conditions. The secretion function of pancreatic juice after fat meal may decrease with age.
[关键词] 胰腺;胰腺外分泌功能;胰液频率;胰液长度;脂肪餐;电影序列;磁共振胰胆管成像;磁共振成像
[Keywords] pancreas;pancreatic exocrine eunction;pancreatic secretion frequency;pancreatic secretion length;fatty meal;cine-dynamic sequence;magnetic resonance cholangiopancreatography;magnetic resonance imaging

吴巧玲 1   王沄 1   孙照勇 1   胡格丽 2   王一鸣 2   金征宇 1   薛华丹 1*  

1 中国医学科学院北京协和医院放射科,北京 100730

2 飞利浦(中国)投资有限公司北京分公司,北京 100600

通信作者:薛华丹,E-mail:bjdanna95@163.com

作者贡献声明:薛华丹设计本研究的方案,对稿件的重要内容进行了修改,获得了中央高水平医院临床科研业务费的资助;吴巧玲起草和撰写稿件,获取、分析及解释本研究的数据;王沄、孙照勇、胡格丽、王一鸣获取及解释本研究的数据,对稿件的重要内容进行了修改;金征宇指导和管理本研究,对稿件的重要内容进行了修改;全部作者都同意发表最后的修改稿,同意对本研究的所有方面负责,确保本研究的准确性和诚信。


基金项目: 中央高水平医院临床科研专项 2022-PUMCH-B-069
收稿日期:2023-04-06
接受日期:2023-08-09
中图分类号:R445.2  R576 
文献标识码:A
DOI: 10.12015/issn.1674-8034.2023.09.014
引用本文:吴巧玲, 王沄, 孙照勇, 等. 采用磁共振2D-MRCP电影成像无创评估胰腺外分泌功能的可行性研究[J]. 磁共振成像, 2023, 14(9): 81-85. DOI:10.12015/issn.1674-8034.2023.09.014.

0 前言

       胰腺外分泌功能检查对于评估胰腺生理功能,诊断胰腺外分泌功能不全相关疾病以及指导治疗具有重要意义[1, 2, 3]。胰腺外分泌功能的检查方法可分为直接方法和间接方法[4]。直接检测法可通过十二指肠插管,内镜下观察促胰液素、促胰液素-盲肠素等刺激后胰液流量的变化,然而,由于内镜检查需要麻醉和镇静,并且插管涉及患者耐受问题,所以直接检测法在临床应用中受限[5, 6, 7]。间接检测方法包括常规血清学检测、粪便脂肪检测、粪便酶检测、呼气试验和特定物质的尿液分析[8, 9, 10]。虽然间接检查是无创的,但其结果容易受到中间代谢过程的影响。实际上,间接检查仅在胰腺外分泌功能严重受损时才有效[11, 12]

       近年来,随着磁共振胰胆管成像(magnetic resonance cholangiopancreatography, MRCP)的发展,ITO等[13]发现,在生理条件下,使用空间选择性反转恢复(inversion pulse, IR)脉冲,可以通过连续的MRCP序列无创地观察胰液的生理流动。既往也有研究静脉注射胰泌素后采用MRI方法检测胰液分泌长度和频率的变化,从而可间接反映胰腺外分泌功能[14, 15],然而由于胰泌素的购买限制,该检查方法未得到广泛应用。因此,寻找类似于胰泌素的刺激物,并探索刺激物对胰腺外分泌功能的影响规律对MRCP动态观察胰腺外分泌功能障碍的广泛应用具有很大临床价值。众所周知,食物的摄入可刺激胰液的分泌,但是食物对胰液分泌的刺激规律可能与胰泌素存在不同。因此,本研究招募了健康志愿者,采用2D-MRCP电影序列检测志愿者口服摄入油煎鸡蛋前后的生理状态下胰液分泌的变化。本研究的目的一方面是探究2D-MRCP 电影序列动态观察胰液分泌情况的可行性,另一方面是探索脂餐后胰腺分泌功能的变化情况,以及脂餐后胰液分泌与年龄的关系。

1 材料和方法

1.1 研究对象

       本前瞻性研究遵守《赫尔辛基宣言》,得到中国医学科学院北京协和医院伦理委员会批准,所有受试志愿者均知情同意,伦理批准文号为:K23C0133。纳入标准:(1)年龄在18岁及以上的健康受试者;(2)无胰胆管疾病或糖尿病病史;(3)正常饮食,近期无药物使用史;(4)不存在MRI检查禁忌证,如起搏器,金属植入物。排除标准:(1)受试者屏气不佳,导致图像质量很差;(2)经扫描发现存在胰胆管占位性病变,影响胰液胆汁排泄者。根据年龄将受试志愿者分为三组:第一组年龄≤30岁,第二组年龄>30岁并≤60岁,第三组年龄>60岁。

1.2 图像采集

       所有健康志愿者都在飞利浦3.0 T MRI扫描仪(Ingenia CX, Philips Healthcare, Best, Netherlands)上采用腹部16通道相控阵列线圈扫描,扫描序列为2D-MRCP动态电影序列。检查前均空腹4~6 h且进行屏气训练。

       首先,采集一个常规的2D-MRCP冠状位图像作为电影序列的参考图像。该序列的扫描层面平行胰管设置,目的是找到显示胰管胆管最佳的冠状层面。其次,在参考图像的基础上设置2D-MRCP电影序列。在垂直于主胰管的胰腺头部设置空间选择性反转脉冲,该脉冲可以抑制背景静态胰液信号,使图像上仅显示流动胰液信号。在电影序列采集的过程中,每次屏气间隔15 s(其中包括4 s的屏气采集时间和11 s的呼吸休息时间),重复屏气采集20次,总共耗时5 min,作为该志愿者的胰腺外分泌基础状态。随后,给志愿者口服脂肪餐(9克油煎3个鸡蛋),立即在餐前扫描序列的基础上进行重复扫描。在餐后,连续屏气扫描60次,总共耗时15 min,获得60张动态图像。该序列用于观察脂餐后胰液分泌的动态变化,并与基础分泌状态比较。电影序列扫描参数:TR 6807.0 ms,TE 760.0 ms,FOV 250 mm×269 mm,翻转角90°,体素0.80 mm×1.01 mm×40.00 mm,重建像素0.51 mm×0.51 mm×0.51 mm,层厚40 mm,空间反转脉冲层厚20 mm,脉冲重复时间2300.0 ms,脉冲反转时间202.4 ms,激励次数1,回波链长度178,屏气扫描时间4 ms,餐前屏气次数20次,餐后屏气次数60次,脂肪抑制采用频率衰减反转恢复序列(spectral attenuated inversion recovery, SPAIR)。

1.3 数据测量

       本研究由两名放射科腹部诊断医师(均为具有五年诊断经验的主治医师)对每个电影序列图像中主胰管的目标图像区域进行胰液分泌频率和胰液流入长度的测量(图1)。每位志愿者脂餐前后的胰液分泌频率和长度为两位医师测量结果平均值。根据既往研究测量经验[16]将胰液分泌的频率定义为在电影动态MRCP扫描期间胰液流入目标成像区域的次数。平均测量的分泌频率定义为所有志愿者的胰液分泌频率之和除以该组中的志愿者总数。胰液分泌的平均测量长度也以相同的方式定义。比较脂餐前后胰液频率和长度的变化,并绘制点图观察脂餐后胰液分泌频率和长度的变化趋势。测量脂餐前后胰管管径大小,探究胰腺分泌的长度与胰管管径的关系。

图1  女,60岁,健康志愿者,采用二维磁共振胰胆管成像(2D-MRCP)电影序列扫描的脂餐前后胰液分泌图像。测量胰头部两个平行线之间胰液分泌的距离作为该志愿者本次屏气胰液分泌的长度,且记录频率一次。1A:脂餐前施加空间反转脉冲区域可见少量或无胰液分泌(平行蓝线之间宽度为20 mm的区域);1B:脂餐后施加空间反转脉冲区域可见明显胰液分泌(平行蓝线之间宽度为20 mm的区域)。
Fig. 1  Female, 60-year-old, healthy volunteers, images of underwent dynamic two-dimensional magnetic resonance cholangiopancreatography (2D-MRCP) with 20 mm width spatially selective IR pulse before and after fatty meal. Measure the distance between the two parallel lines at the head of the pancreas and measure the length of the volunteer's breath holding pancreatic juice secretion, and record the frequency once. 1A: No noticeable pancreatic juice secretion before a fatty meal (the area of 20 mm width between the parallel blue lines). 1B: The length of pancreatic juice secretion after a fatty meal (the area of 20 mm width between the parallel blue lines).

1.4 统计学方法

       采用SPSS 21.0统计学软件进行统计学处理。对于频率(计数资料)使用百分数进行差异比较。对于胰液长度(计量资料),首先使用Kolmogorov-Smirnov检验方法做正态性检验。如果符合正态分布,则用(x¯±s)表示,并采用配对t检验法比较脂餐前后胰液分泌长度的差异和脂餐前后胰管管径的差异;如果不符合正态分布,则使用MQ1,Q3)表示,采用秩和检验比较脂餐前后胰液分泌长度的差异和脂餐前后胰管管径的差异。采用Kruskal-Wallis法比较脂餐后胰液分泌平均频率和平均长度与年龄之间的关系。P<0.05表示差异具有统计学意义。

2 结果

2.1 一般资料

       2021年1月至2021年10月期间,我们采集了36名健康志愿者的数据,其中男13人,女23人,年龄22~68(45.68±10.68)岁。按年龄分组情况:第一组5人,其中男1人,女4人;第二组20人,其中男8人,女12人;第三组11人,其中男4人,女7人。为保证病例检查时间的统一性,避免胰液分泌是否受昼夜的影响,本研究所有志愿者均在本单位科研机18∶00~21∶00时扫描。

2.2 测量结果

       所有志愿者的图像上均可以清晰观察到施加了选择性反转恢复脉冲的目标区域,背景信号被抑制,而实时分泌的动态胰液呈高信号。脂餐前,在目标区域可以观察到少量或者无流动胰液信号,而脂餐后目标区域可以明显观察到胰液高信号,如图1所示。脂餐前后胰液分泌的平均频率和长度测量结果见表1。测量结果表明口服脂餐(油煎鸡蛋)可以刺激胰液分泌,脂餐后的胰液分泌频率和长度较脂餐前明显增加。志愿者脂餐前后胰管管径范围均为1~3 mm,脂餐前胰管平均管径为(2.01±1.55)mm,脂餐后胰管平均管径为(2.13±0.92)mm,差异具有统计学意义(t=0.582,P<0.001)。此外,通过散点图我们可观察到在8 min 15 s至9 min 15 s之间胰液分泌长度为(16.79±1.31)mm,该时间段内的分泌长度高于平均值(15.34±4.61)mm,而胰液分泌的峰值长度出现在第13 min,如图2图3所示。

图2  36名健康志愿者平均脂餐后的胰液分泌频率折线图。随着时间动态观察胰液分泌频率未见明显集中规律。
Fig. 2  Curve of pancreatic juice secretion frequency of 36 healthy volunteers after a fatty meal over time. No concentration trend over time is found.
图3  36名健康志愿者平均脂餐后的胰液分泌长度折线图。随着时间动态观察胰液分泌长度变化,发现在餐后8 min 15 s至9 min 15 s区间胰液分泌长度均持续高于平均分泌长度,在餐后13 min胰液平均分泌长度达到峰值。
Fig. 3  Curve of pancreatic juice length rate of 36 healthy volunteers after a fatty meal over time. The lengths of pancreatic juice secretion are higher than the average value between 8 min 15 s and 9 min 15 s, the peak time is 13 min.
表1  脂餐前后的胰腺分泌平均频率和长度对比结果
Tab. 1  Changes in average frequency and length of pancreatic secretion before and after fat meal

2.3 分组统计分析结果

       组间两两比较发现第一组与第二、三组之间胰液分泌长度和频率比较差异均具有统计学意义(P<0.001),第二组和第三组之间胰液分泌长度和频率比较差异不具有统计学意义(P=0.477、0.316),具体结果见表2

表2  不同年龄组志愿者脂餐后的胰液分泌长度和频率对比结果
Tab. 2  Comparison of pancreatic juice secretion length and frequency after fat meal in volunteers of different age groups

3 讨论

       本研究采用2D-MRCP动态电影序列定量观测胰液分泌情况,通过测量口服脂餐前后胰液分泌频率和长度的变化,实现生理状态下对胰腺外分泌功能的无创评估。与先前的研究使用MRCP序列检测静脉注射胰泌素后胰腺外分泌功能的方法比较[17, 18, 19],本研究创新性地提出采用口服油煎鸡蛋作为胰液分泌刺激物,选择了更接近生理状态的口服脂餐,能够真实反映胰腺在生理状态下的分泌功能。这一方法对于慢性胰腺炎患者的长期随访和胰十二指肠手术患者术后胰腺分泌功能改善的评估具有重要的临床价值。此外,对于在胰岛素购买和使用受限的国家和地区,本研究提供了一种无创可视化检测方法。

3.1 膳食种类对胰腺液分泌情况的影响

       先前的研究已经表明,膳食刺激能够迅速改变胰液分泌功能,并且胰液分泌量在膳食刺激后的时间窗口中呈现出不同的变化趋势[20, 21, 22]。本研究选择油煎鸡蛋作为刺激物,与先前研究中使用的液体饮料等不同。通过散点图发现脂餐后胰液分泌频率和长度的变化趋势特征不明显。然而,胰液分泌量达到峰值的时间为第13 min,这种时间差异主要是由于所选膳食类型不同,胰液分泌时间受食物在胃内消化排空进入十二指肠的速率影响。与液体相比,固体食物在胃内停留的时间更长,因此胰液分泌量到达峰值的时间比液体更晚[23, 24, 25]

       为了更准确地反映固态餐后胰液分泌的整体变化趋势,本研究将脂餐后动态屏气次数从餐前的20次延长到餐后的60次,并将采集时间从餐前的5 min延长至餐后的15 min。我们选择油煎鸡蛋作为刺激物的原因是固态食物在胃内停留的时间更长,因此能更稳定地观察胰液分泌量的变化趋势。这进一步突显了口服脂肪餐作为胰液分泌刺激物的可行性和适用性,并对了解固态餐后胰液分泌的整体变化趋势具有重要意义。

3.2 年龄组别和胰腺液的关系

       根据先前的研究,胰液外分泌功能随着年龄增长而明显下降[26]。本研究通过对志愿者按年龄分组进行研究,发现30岁以下志愿者在口服脂餐后具有较高的胰液外分泌水平,而30岁至60岁年龄组和60岁以上年龄组之间的差异不明显。这种差异的主要原因是胰液外分泌水平受多种因素影响,包括胰管形态、饮食习惯、胃肠道健康状况、胃肠道蠕动力以及各种消化酶和激素分泌的差异[27]。然而,由于所收集的各组志愿者人数和性别不均衡,对各个年龄段的比较结果仅可作为后续研究的参考。今后,我们将在新设备上继续扩大样本量,并平衡各年龄组的人数和性别,进一步探究口服脂餐后胰液外分泌功能与年龄的关系。

3.3 局限性

       本研究还存在一些局限性需要注意。首先,尽管该方法能够可视化观察胰液分泌量的变化情况,但无法检测胰液成分(如碳酸氢盐浓度和淀粉酶)的变化,因此无法准确评估胰腺外分泌功能的等级;其次,胰液分泌功能受个体差异较大,本研究受设备更新的限制,样本量相对较小,对于总结餐后胰液分泌变化趋势仍需进一步验证。为了克服这些局限性,今后的研究可以在新设备上增大样本量,以获得更具代表性的数据,并进一步探索胰腺外分泌的规律。此外,可以考虑结合其他相关指标进行综合评估,以更全面地了解胰腺外分泌功能的情况。

4 结论

       本研究验证了2D-MRCP动态电影序列进行无创评估生理状态下胰腺外分泌功能的可行性,并表明采用口服脂餐(油煎鸡蛋)可以有效刺激胰液分泌。本研究为无创可视化检测胰液分泌提供了一种新方法,特别适用于慢性胰腺炎患者的长期随访和胰十二指肠手术后胰腺分泌功能的评估。此外,脂餐作为胰液分泌刺激物的使用,对于胰泌素购买和使用受限的国家或地区具有重要意义。

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