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   复旦学报(医学版)  2022, Vol. 49 Issue (4): 574-581      DOI: 10.3969/j.issn.1672-8467.2022.04.015
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Care kV技术在双源CT胸痛三联CT血管造影中对图像质量及辐射剂量的影响
王坤1 , 金倞1 , 李骋1 , 田全凯1 , 张渌恺1 , 李铭1,2     
1. 复旦大学附属华东医院放射科 上海 200040;
2. 复旦大学医学功能与分子影像研究所 上海 200040
摘要目的 探讨新一代双源CT结合Care kV技术在胸痛三联CT血管造影(triple rule out CT angiography,TRO-CTA)中对图像质量及辐射剂量的影响。方法 回顾性收集2021年3月至9月于复旦大学附属华东医院胸痛中心就诊、拟行TRO-CTA检查的90例患者作为研究对象,根据患者不同的扫描方式分为A、B两组。A组CT扫描管电压由Care kV技术决定,B组采用固定管电压120 kV,比较两组图像质量及辐射剂量。结果 A组平均CT容积剂量指数(CT dose index volume,CTDIvol)显著低于B组[(20.42±9.60)mGy vs.(32.27±13.41)mGy,P < 0.001)]。A组的平均剂量长度乘积(dose length product,DLP)显著低于B组[(525.28±240.12)mGy×cm vs.(944.20±408.36)mGy×cm,P < 0.001)]。因此,A组的平均有效辐射剂量(effective dose,ED)显著低于B组[(7.35±3.36)mSv vs.(13.22±5.72)mSv,P < 0.001)]。左前降支远段及左回旋支远段除外,A组中其余血管CT值均显著高于B组(P < 0.05)。A组图像噪声显著高于B组(15.79±3.81 vs. 11.37±3.40,P < 0.001)。除左前降支远段以外两组血管节段信噪比(sign-to-noise ratio,SNR)差异均无统计学意义。A组肺动脉、主动脉噪声比(contrast-to-noise ratio,CNR)与B组差异无统计学意义,但A组冠脉CNR普遍高于B组。A、B两组图像肺动脉、主动脉及冠脉主观评分差异无统计学意义。结论 在新一代双源CT上采用Care kV技术进行TRO-CTA检查,在满足图像诊断质量的同时,可以显著降低辐射剂量。
关键词Care kV技术    双源CT    胸痛三联CT血管造影(TRO-CTA)    图像质量    辐射剂量    
Effect of Care kV technology on image quality and radiation dose in dual-source CT triple rule out CT angiography for chest pain
WANG Kun1 , JIN Liang1 , LI Cheng1 , TIAN Quan-kai1 , ZHANG Lu-kai1 , LI Ming1,2     
1. Department of Radiology, Huadong Hospital, Fudan University, Shanghai 200040, China;
2. Institute of Functional and Molecular Medical Imaging, Fudan University, Shanghai 200040, China
Abstract: Objective To investigate the effect of new generation dual source CT combined with Care kV technology on image quality and radiation dose in triple rule out CT angiography (TRO-CTA) for chest pain. Methods Ninety patients who attended the Chest Pain Center of Huadong Hospital, Fudan University from Mar to Sep 2021 and were proposed for TRO-CTA were retrospectively collected. They were divided into two groups A and B according to the different scanning methods. The tube voltage of CT scan in group A was determined by the Care kV technique, while group B used a fixed tube voltage of 120 kV. The image quality and radiation dose were compared between the two groups. Results The mean CT dose index volume (CTDIvol) was significantly lower in group A than in group B [(20.42±9.60) mGy vs. (32.27±13.41) mGy, P < 0.001)].The mean dose length product (DLP) in Group A was significantly lower than that in Group B [(525.28 ± 240.12) mGy×cm vs. (944.20±408.36) mGy×cm, P < 0.001)].Thus, the mean effective radiation dose (ED) was significantly lower in group A than in group B [(7.35 ± 3.36) mSv vs. (13.22 ± 5.72) mSv, P < 0.001)].The CT values of all vessels in group A were significantly higher than those in group B (P < 0.05), except for the distal segment of the left anterior descending and the distal segment of the left circumflex. Image noise was significantly higher in group A than in group B (15.79±3.81 vs. 11.37±3.40, P < 0.001).The differences in signal-to-noise ratio of vessel segments between the two groups were not statistically significant except for the distal segment of the LAD. The differences in contrast-to-noise ratio of pulmonary artery and aorta in group A and group B were not statistically significant, but the CNR of coronary artery in group A was generally higher than that in group B.The differences in subjective scores of pulmonary artery, aorta and coronary artery in images from group A and B were not statistically significant. Conclusion The use of Care kV technology for TRO-CTA angiography of chest pain on a new generation dual-source CT can significantly reduce radiation dose while guaranteeing the diagnostic quality of the images.
Key words: Care kV technology    dual-source CT    triple rule out CT angiography (TRO-CTA)    image quality    radiation dose    

急性胸痛是急诊科最常见的症状之一,然而区分急性冠状动脉综合征(acute coronary syndrome,ACS)和其他原因引起的胸痛是急诊科经常遇到的难题[1-2]。具体来说,主动脉夹层(aortic dissection,AD)和肺栓塞(pulmonary embolism,PE)是两种与ACS症状相似的急性疾病,其发病迅速,死亡率较高,严重威胁患者的生命安全[3]。胸痛三联CT血管造影(triple rule out CT angiography,TRO-CTA)是一种快速、无创的检查方法,在评估冠状动脉的同时可视化肺动脉、胸主动脉及胸腔内其他结构[4-6]

然而,与冠状动脉CT血管造影(coronary computed tomography angiography,CCTA)相比,TRO-CTA需要从主动脉弓上方一直扫到膈顶上方,扫描长度增加,因此辐射剂量较高[7]。一项研究表明[8],在第一代双源CT上使用120 kV管电压进行TRO-CTA,其辐射剂量高达22.0 mSv。又有研究表明[9],CT检查所产生的高电离辐射会导致人体DNA双链断裂进而染色体发生变异,导致患者患癌风险增加。因此,如何在保证CT图像质量的同时,最大限度地减少辐射剂量,成为人们普遍关注的问题。在过去十年,随着CT技术的快速发展,已经开发出很多新技术来减少辐射剂量,例如宽体探测器扫描[10]、迭代重建算法[11]以及Care kV技术。但目前还未有关于Care kV技术在TRO-CTA检查中的应用报道,本研究旨在探讨双源CT结合Care kV技术在TRO-CTA检查中对图像质量以及辐射剂量的应用价值。

资料和方法

研究对象   回顾性收集复旦大学附属华东医院影像归档与通信系统中(picture archiving and communication systems,PACS)自2021年3月至9月于胸痛中心就诊、拟行TRO-CTA检查的90例患者作为研究对象。根据患者不同的扫描方式进行分组,其中45例患者采用管电流采用Care Dose4D技术,参考电流:320 mAs。管电压采用Care kV技术,自动调节管电压(70~140 kV),参考电压:100 kV,作为A组。另有45例患者管电流采用Care Dose4D技术,参考电流:320 mAs,管电压采用固定电压120 kV,作为B组。A组患者年龄为30~83岁,B组患者年龄为39~95岁。纳入标准:急性胸痛患者,临床疑诊为ACS、PE或AD,且出具CT诊断报告的患者。排除标准:扫描参数未使用上述两组扫描条件的TRO-CTA检查患者。所有患者均签署CT增强检查知情同意书。

图像采集   所有患者均采用新一代双源CT(Somatom Drive,德国Siemens Healthcare公司)进行扫描,准直器2 mm×64 mm×0.6 mm,机架转速0.28 s/rot。两组重建层厚均为0.75 mm,层间距0.5 mm。两组扫描范围均由头部至足部方向从主动脉弓上方扫至膈顶上方,扫描模式均为回顾性心电门控触发扫描方式。两组均采用实时心电脉冲(ECG-pulsing)技术,全剂量曝光范围为30%~80% R-R间期。注射方案两组统一95 mL碘对比剂(三代显,350 mgI/mL),第一期注射流速4.5 mL/s,共注射45 mL,第二期流速4.0 mL/s注射50 mL,第三期盐水3.5 mL/s注射30 mL[12]。运用对比剂团注示踪技术,触发阈值100 HU,延迟时间为7 s。所有图像均传送至AW4.4(美国GE Healthcare公司)进行图像后处理及测量分析。

图像客观质量评价   由一名影像诊断经验丰富的医师在工作站分别测量各组横断位图像上主肺动脉干、左肺动脉干、右肺动脉干、右冠状动脉、左前降支、左回旋支、升主动脉根部、主动脉弓、降主动脉、主动脉根部同层面的竖脊肌以及冠脉周围脂肪组织的平均CT值和SD值,并分别计算信噪比和对比噪声比[13]。主动脉根部感兴趣区(region of interest,ROI)的SD值作为图像噪声,图像信噪比(sign-to-noise ratio,SNR)=CT值/噪声,图像的对比噪声比(contrast-to-noise ratio,CNR)=(CT值-血管周围脂肪组织CT值)/噪声[14]。肺动脉、主动脉ROI面积设置为90 mm2,其他区域设置为1 mm2,每个指标测量3次取平均值,测量时为保证结果的准确性,并尽量避开斑块及钙化区域。

图像主观质量评价   由2名具有3年以上工作经验的放射科医师,采用4分法对图像进行整体评分,存在分歧时协商统一。4分为优秀,血管显示清晰,血管边缘光滑、锐利,无伪影;3分为良好,血管显示清晰,血管边缘模糊,图像运动伪影较小;2分为一般,血管显示模糊,图像运动伪影明显;1分为差,动脉血管显差,严重运动伪影干扰,无法诊断[15]

辐射剂量   所有90例患者的辐射剂量资料从PACS中的患者剂量表中获得,记录患者TRO-CTA检查时的CTDIvol、DLP以及ED。其中ED=DLP×转换因子[K=0.014 mSv/(mGy·cm)][16]

统计学分析   用SPSS 26.0软件进行统计分析。计量资料若符合近似正态分布,则用x±s描述,若不符合近似正态分布,则用中位数及四分位数间距进行描述,表示为M(P25,P75)。计数资料采用绝对数值和相应频率百分比描述。符合正态分布的计量资料采用独立样本t检验,不符合正态分布的计量资料采用非参数秩和检验,计数资料采用χ2检验。2名医师对图像质量评分的一致性采用Kappa检验,κ值0.21~0.40表示一致性较差,0.41~0.60表示一致性中等,0.61~0.80表示一致性良好。P < 0.05为差异有统计学意义。

结果

患者基本资料   A、B两组的中位年龄分别为64.0(60.0,69.0)岁、65.0(59.5,75.0)岁,A组中男性患者24例(53.3%),女性患者21例(46.7%);B组男性患者25例(55.6%),女性患者20例(44.4%),两组患者平均身高分别为(1.68±0.07)m、(1.65±0.08)m,平均体重分别为(67.5±10.1)kg、(66.2±11.6)kg,平均BMI分别为(23.8±2.8)kg/m2、(24.1±3.0)kg/m2,平均心率为(70±10)次/分、(75±14)次/分,基本资料均无显著差异(表 1)。

表 1 两组患者基本资料及辐射剂量 Tab 1 Patient characteristics and radiation dose in the two groups[M(P25, P75), x±s or n(%)]
Prameters Group A Group B t/z P
Male/Female 24/21 25/20 0.045 0.832
Age(y) 64.0(60.0,69.0) 65.0(59.5,75.0) -1.377 0.168
Height(m) 1.68±0.07 1.65±0.08 1.948 0.055
Weight(kg) 67.5±10.1 66.2±11.6 0.589 0.557
BMI(kg/m2 23.8±2.8 24.1±3.0 -0.545 0.587
Heart rate(bpm) 70 ± 10 75±14 -1.842 0.069
Tube voltage(kV) 86.087 < 0.001
  90 31(68.89) 0
  100 9(20.00) 0
  110 4(8.89) 0
  120 1(2.22) 45(100)
CTDIvol(mGy) 20.42±9.60 32.27±13.41 -4.822 < 0.001
DLP(mGy×cm) 525.28±240.12 944.20±408.36 -5.257 < 0.001
ED(mSv) 7.35±3.36 13.22±5.72 -5.257 < 0.001
BMI:Body mass index;CTDIvol:CT dose index volume;DLP:Dose length product;ED:Effective dose.

诊断结果   根据CT诊断报告,诊断疾病情况如下:A组中,冠状动脉狭窄者20例,冠状动脉支架术后2例,主动脉瓣钙化2例,升主动脉增宽1例,肺动脉增宽1例。B组中,冠状动脉狭窄者23例,冠状动脉支架术后2例,右冠状动脉中段主动脉瘤形成1例,主动脉瓣钙化2例,主动脉粥样硬化并斑块形成1例,升主动脉增宽1例。

辐射剂量   A组中,使用90 kV进行扫描的患者31人,100 kV的9人,110 kV的4人,120 kV 1人;B组中,45例患者均用120 kV管电压进行扫描。A组平均CTDIvol显著低于B组[(20.42±9.60)mGy vs.(32.27±13.41)mGy,P < 0.001)]。同样,A组的平均DLP显著低于B组[(525.28±240.12)mGy×cm vs.(944.20±408.36)mGy×cm,P < 0.001)]。因此,A组的平均ED显著低于B组[(7.35±3.36)mSv vs.(13.22±5.72)mSv,P < 0.001)]。A组与B组相比,有效辐射剂量减少了44.4%。相关结果见表 1

图像质量评价   左前降支远段及左回旋支远段除外,A组中其余血管CT值均显著高于B组(P < 0.05),虽然B组左前降支远段及左回旋支CT值高于A组,但两组间差异无统计学意义。A组图像噪声显著高于B组(15.79±3.81 vs. 11.37±3.40,P < 0.001)。除左前降支远段以外两组血管节段SNR差异均无统计学意义。A组肺动脉、主动脉CNR与B组差异无统计学意义,但A组冠脉CNR普遍高于B组。2名医师对于主观质量评分的一致性好(Kappa=0.637,P < 0.05),在一致性较好的情况下,采用年资较高医生所评得分作为最终评价指标。A、B两组图像肺动脉、主动脉及冠脉主观评分差异无统计学意义(表 2)。以2例BMI相似患者为例,其TRO-CTA检查结果如图 1所示。

表 2 两组图像评价指标比较 Tab 2 Comparison of image evaluation indexes between the two groups[M(P25, P75) or x±s]
Indexes Group A Group B t/z P
CT value(HU)
  PT 492.26±21.23 404.18±14.66 3.414 0.001
  LPA 464.17±133.47 384.11±101.45 3.203 0.002
  RPA 457.31(359.58,580.03) 364.30(323.86,440.47) -3.248 0.001
  AO 483.26±87.92 371.78±74.00 6.508 < 0.001
  AA 532.42(456.91,572.67) 363.09(320.62,407.74) -6.274 < 0.001
  DA 490.25±90.74 359.12±73.29 7.542 < 0.001
  LMCA-P 501.62±95.65 374.66±61.61 7.485 < 0.001
  LAD-M 358.86(288.77,439.29) 308.58(281.73,342.47) -2.373 0.018
  LAD-D 213.08±88.66 237.50±57.44 -1.550 0.125
  LCX-M 267.05±98.05 259.87±67.32 3.156 0.002
  LCX-D 260.50(199.00,305.05) 269.08(207.71,300.60) 0.405 0.768
  RCA-P 506.67(417.81,555.14) 369.53(336.78,423.27) -4.616 < 0.001
  RCA-M 457.43±113.60 361.73±80.74 4.606 < 0.001
  RCA-D 444.94±129.13 337.06±100.31 4.426 < 0.001
  ESM 48.84±13.22 64.88±10.83 -6.295 < 0.001
  PVAT -102.94±6.37 -108.77±13.32 -5.387 0.010
Image noise 15.79±3.81 11.37±3.40 5.803 < 0.001
SNR
  PT 36.83±1.41 38.79±1.73 -0.878 0.382
  LPA 31.98(26.60,37.79) 29.08(24.76,33.38) 1.738 0.143
  RPA 25.12(20.66,35.76) 28.91(23.63,36.84) -1.812 0.070
  AO 56.47(44.32,90.84) 61.69(51.13,83.17) -1.392 0.164
  AA 43.32±11.43 39.30±10.47 -1.570 0.086
  DA 36.41±11.35 36.29±10.03 0.053 0.958
  LMCA-P 36.46(27.43,47.04) 31.93(27.20,40.45) -1.126 0.260
  LAD-M 12.71(8.86,19.83) 13.97(8.95,22.40) -0.327 0.744
  LAD-D 6.18(4.54,9.26) 8.54(6.87,11.83) -2.974 0.003
  LCX-M 18.14(9.41,28.39) 16.52(11.96,23.45) -0.286 0.775
  LCX-D 8.59(5.76,12.39) 9.05(7.13,13.48) -1.231 0.218
  RCA-P 28.83(19.02,44.13) 27.12(19.91,38.02) -0.690 0.490
  RCA-M 21.97(14.92,32.56) 19.62(13.53,25.84) -0.859 0.390
  RCA-D 20.99±10.36 20.22±12.80 -1.206 0.754
CNR
  PT 56.12(44.90,91.05) 70.18(53.77,91.37) -1.497 0.134
  LPA 52.39(39.65,80.94) 65.24(49.56,86.29) -1.594 0.111
  RPA 54.58(39.57,92.67) 67.94(47.12,88.46) -1.376 0.169
  AO 56.47(44.32,90.84) 61.69(51.13,83.17) -0.722 0.470
  AA 60.57(46.94,95.05) 59.18(51.24,78.36) -0.190 0.850
  DA 59.94(44.56,93.00) 58.60(49.60,80.66) -0.020 0.984
  LMCA-P 105.53±23.27 81.42±20.92 -4.709 < 0.001
  LAD-M 80.91±21.00 70.71±16.68 2.550 0.013
  LAD-D 55.02±17.60 57.86±12.98 -0.870 0.387
  LCX-M 87.81±22.04 74.76±20.85 -3.095 0.005
  LCX-D 64.41±18.50 62.24±18.74 0.553 0.582
  RCA-P 102.83±23.45 83.46±23.51 -4.039 < 0.001
  RCA-M 97.90±24.89 79.06±21.90 -3.619 < 0.001
  RCA-D 96.07±28.20 74.65±22.08 4.012 < 0.001
Subjective
  Pulmonary artery 3.0(2.0,4.0) 3.0(2.0,3.0) -1.817 0.069
  Aorta 3.0(3.0,4.0) 3.0(3.0,3.0) -3.765 0.052
  Coronary artery 3.0(3.0,3.0) 3.0(2.0,3.0) -1.945 0.154
PT:Pulmonary trunk;LPA:Left pulmonary artery;RPA:Right pulmonary artery;AO:Aortic root;AA:Aortic arch;DA:Descending aorta;SNR:Signal-to-noise ratio;CNR:Contrast-to-noise ratio;LMCA-P:Proximal left main coronary artery;LAD-M:Middle left anterior descending;LAD-D:Distal left anterior descending;LCX-M:Middle left circumflex;LCX-D:Distal left circumflex;RCA-P:Proximal right coronary artery;RCA-M:Middle right coronary artery;RCA-D:Distal coronary right artery;ESM:Erector spinae muscle;PVAT:Perivascular adipose tissue.
A-D: Patient in group A, BMI 23.40 kg/m2, tube voltage 90kV.A: VR image of coronary tree.B: Curved multiplannr reformation image of left anterior descending coronary artery. C: Coronal reconstruction image of pulmonary artery.D: Sagittal reconstruction image of the thoracic aorta. E and F: Patient in group B, BMI 22.51 kg/m2, tube voltage 120 kV.E: VR image of coronary tree. F: Curved multiplannr reformation image of right coronary artery.G: Coronal reconstruction image of pulmonary artery.H: Sagittal reconstruction image of the thoracic aorta. 图 1 两组TRO-CTA图像比较 Fig 1 Comparison of TRO-CTA images between the two groups
讨论

在CT扫描中,辐射剂量往往与图像质量呈负相关,Care kV技术是近年来出现的一种解决辐射剂量与图像质量之间矛盾的技术[17-18]。Care kV技术在扫描患者的定位像之后,自动判断患者其体型,根据预设的图像质量水平确定扫描所需kV值,同时计算所需管电流的基准值以及变化曲线[19-21]

胸痛三联CT血管造影(TRO-CTA)旨在一次检查中同时评估急性冠脉综合征、主动脉夹层及肺栓塞[22]。但该检查因扫描长度较长,因此辐射剂量与普通冠脉CT血管造影相比大幅增加。Takakuwa等[6]研究发现,在64层螺旋CT上采用回顾性心电门控扫描模式进行一次TRO-CTA检查,患者所受平均有效辐射剂量为18 mSv。而高剂量电离辐射可能会导致人体染色体DNA链损伤[9]。因此在本研究中我们对新一代双源CT结合Care kV技术在TRO-CTA中的应用进行了初步的临床评估,重点关注辐射剂量和图像质量。较低的管电压可以降低X线球管产生的X线光谱的平均能量[23],与固定管电压120 kV相比,在不改变检查流程的情况下,采用Care kV技术在新一代双源CT进行TRO-CTA可以显著降低辐射剂量(约44%),同时保证良好的图像诊断质量。Mangold等[24]采用Care kV技术进行胸腹主动脉CT血管造影,与标准120 kV管电压相比,剂量减少了约41%,这与我们的结果相似。

在A组中,除了左前降支、左回旋支远段,其余血管节段CT均明显高于B组,这是因为在较低的管电压下,在碘等原子序数较高的元素中光电效应增强,因此,碘对比剂在血管内的增强程度会随着管电压的降低而升高[25]。所以在碘对比剂注射方案相同的情况下,A组血管节段CT值普遍大于B组。但是由于肺动脉与主动脉、冠脉达峰时间存在差异,因此确定一套最佳的碘对比剂注射方案同时可视化肺动脉、胸主动脉及冠状动脉仍然是一个挑战[26]

在本研究中,虽然A组图像噪声与B组相比明显增加(15.79±3.81 vs. 11.37±3.40,P < 0.001),这是因为A组管电压降低之后,X射线穿透能力降低,因此图像噪声增加[27],但图像质量与B组相比并未有显著差异,并且满足诊断要求。降低管电压之后虽然图像噪声增加,但是血管CT值增加,两组图像信噪比与对比噪声比保持相似,甚至A组冠脉图像CNR优于B组,保持了图像质量的一致性。

本研究还比较了两组图像信噪比、对比噪声比不同医师主观评分之间的差异。两组图像除了左前降支远段其余血管节段SNR,肺动脉与胸主动脉CNR均无显著差异(表 2),A组冠脉CNR普遍高于B组(表 2),两名医师对两组图像的主观评分均无显著差异。这证明采用Care kV技术进行TRO-CTA检查,在降低剂量的同时,并未牺牲图像质量。同时,根据CT影像诊断报告,两组患者中对于冠状动脉、肺动脉以及主动脉的疾病诊断结果类似,使得胸痛的多种病因能够同时准确地得到评估,说明Care kV技术结合双源CT进行TRO-CTA检查,诊断结果并不亚于常规固定管电压扫描方案,同时大幅降低辐射剂量,因此在急性胸痛患者中具有较高的临床应用价值。

本研究有以下几点局限性:第一,未应用其他降低辐射剂量技术,例如大螺距回顾性心电门控扫描,但此技术对心率要求较高,在急性胸痛患者中实际应用较少。第二,只从客观和主观两个方面评价了图像质量,并未将有创冠脉造影结果与TRO-CTA检查进行比较,因此在诊断准确性方面仍需进一步的研究。第三,两组病例数较少,且均来自同一家医院,未来将进一步扩大样本量进行多中心研究以确保结果的可信度。第四,采用固定95mL碘对比剂三期注射方案,并未根据体重、BMI等个体差异量化碘对比剂,因此碘对比剂的使用将进一步研究。

综上所述,在新一代双源CT上采用Care kV技术进行胸痛三联CT血管造影检查,在满足图像诊断质量的同时,可以显著降低辐射剂量。

作者贡献声明   王坤  研究设计,数据搜集及分析,论文撰写。金倞  论文构思、审阅和修订,数据测量及解释。李骋  数据测量,技术指导,提供病例图片。田全凯,张渌恺  数据搜集。李铭  数据分析,项目统筹,论文修订。

利益冲突声明   所有作者均声明不存在利益冲突。

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文章信息

王坤, 金倞, 李骋, 田全凯, 张渌恺, 李铭
WANG Kun, JIN Liang, LI Cheng, TIAN Quan-kai, ZHANG Lu-kai, LI Ming
Care kV技术在双源CT胸痛三联CT血管造影中对图像质量及辐射剂量的影响
Effect of Care kV technology on image quality and radiation dose in dual-source CT triple rule out CT angiography for chest pain
复旦学报医学版, 2022, 49(4): 574-581.
Fudan University Journal of Medical Sciences, 2022, 49(4): 574-581.
Corresponding author
LI Ming, E-mail: minli77@163.com.
基金项目
国家自然科学基金面上项目(61976238);上海市科委科研项目(20Y11902900);上海市“医苑新星”青年医学人才培养资助计划(AB83030002019004)
Foundation item
This work was supported by the General Program of National Natural Science Foundation of China (61976238), the Scientific Research Program of Science and Technology Commission of Shanghai Municipality (20Y11902900) and Shanghai "Rising Stars of Medical Talent" Youth Development Program "Outstanding Youth Medical Talents" (AB83030002019004)

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