Background: The aim of this study was to evaluate the feasibility of a dualbolus protocol, where a first bolus of an intravascular tracer is used to measure perfusion, followed by a second bolus of a freely filtered g...Background: The aim of this study was to evaluate the feasibility of a dualbolus protocol, where a first bolus of an intravascular tracer is used to measure perfusion, followed by a second bolus of a freely filtered gadolinium-containing agent to measure filtration capacity. Methods: The study was conducted in mice subjected to complete unilateral ureteral obstruction (UUO), and sham operated mice were used as controls. Dynamic contrast- en-hanced MRI was performed 2 days after surgery. Results and discussions: Mean signal-time curves of the renal cortex, renal medulla and abdominal aorta were used to calculate the relative renal blood flow (rRBF), relative renal blood volume (rRBV), mean transit time (MTT) and the glomerular transfer rate Ktrans. We demonstrated that kidneys suffering from two days of UUO showed a decrease in cortical as well as medullary rRBF compared to kidneys from sham-operated mice. Further, we found no changes in rRBV and MTT among groups, neither in the cortex nor in the medulla. The renal functional parameter Ktrans showed a tendency (but statistically insignificant) to be reduced in the ob-structed kidney compared to the sham-operated mice. Conclusions: We showed our first experiences with the consecutive use of intra- and extra-vascularly distributed agents in a renal-diseased mouse model, allowing analysis of both functional haemo- dyamics and filtration capacity in kidneys.展开更多
目的 利用MRI影像数据,基于亚型与阶段推断算法(SuStaIn)构建精神分裂症(SCZ)与双相情感障碍(BD)跨诊断的脑萎缩进展亚型框架。方法 纳入190例SCZ与BD患者,以及158名健康对照组。基于其T1WI MRI影像,提取17个感兴趣脑区的灰质体积(GMV)...目的 利用MRI影像数据,基于亚型与阶段推断算法(SuStaIn)构建精神分裂症(SCZ)与双相情感障碍(BD)跨诊断的脑萎缩进展亚型框架。方法 纳入190例SCZ与BD患者,以及158名健康对照组。基于其T1WI MRI影像,提取17个感兴趣脑区的灰质体积(GMV),利用SuStaIn进行亚型与分期建模。利用方差分析评估亚型间临床特征差异,Spearman分析验证临床特征差异及其与模型分期的相关性。结果 SuStaIn模型识别出两类不同的大脑萎缩进展轨迹:小脑主导型(以小脑起始,逐步累及布洛卡区、额叶与岛叶)与前额叶主导型(以额叶起始,扩展至扣带回、颞叶)。前额叶主导型患者在阳性症状评分上显著高于小脑主导型(14.2±5.4 vs. 9.15±4.1,P=0.029)。亚组分析表明:前额叶主导型患者表现出更严重的阳性症状(BD:14.4±5.2 vs. 11.3±4.5,P=0.041;SCZ:8.6±2.8 vs. 7.2±1.7,P=0.038)。两种亚型的小脑(r=-0.169,P=0.007)和前额叶(r=-0.193,P=0.002)GMV随分期推移均呈下降趋势,阳性症状(r=0.331,P=0.012)、阴性症状(r=0.283,P=0.033)及一般症状(r=0.411,P=0.002)的症状严重程度增加。结论基于横断面MRI数据,发现SCZ与BD的两类跨诊断脑萎缩路径,且随分期推移,临床症状加重。结果支持精神障碍为一种具有明确空间-时间进展特征的神经退行性过程。展开更多
目的探索不同亚型注意缺陷多动障碍(attention-deficit/hyperactivity disorder,ADHD)患者脑白质微观结构异常并建立分类模型。方法前瞻性纳入2019年1月-2021年9月就诊于四川大学华西医院的ADHD患者及经广告招募的健康对照者,所有受试...目的探索不同亚型注意缺陷多动障碍(attention-deficit/hyperactivity disorder,ADHD)患者脑白质微观结构异常并建立分类模型。方法前瞻性纳入2019年1月-2021年9月就诊于四川大学华西医院的ADHD患者及经广告招募的健康对照者,所有受试者均接受弥散张量成像扫描。通过全脑基于体素的分析对混合型ADHD(combined subtype of ADHD,ADHD-C)、注意缺陷型ADHD(inattentive subtype of ADHD,ADHD-I)和对照组的各向异性分数(fractional anisotropy,FA)参数图进行组间比较。运用支持向量机分类器及特征选择方法构建个体化ADHD分类模型,并对3组受试者两两之间的分类效能进行检测。结果共纳入26例ADHD-C型、24例ADHD-I型患者及26例健康对照者。3组受试者在双侧颞叶白质矢状层及胼胝体峡部FA值差异有统计学意义(P<0.005),前者表现为ADHD-C型患者<ADHD-I型患者<对照者,后者表现为ADHD-C型患者>ADHD-I型患者>对照者;两组亚型之间的差异点位于右侧额中回白质,表现为ADHD-C型>ADHD-I型。基于FA图的分类模型在对两种亚型患者间的分类预测中效能最高(P<0.05,总体准确率=76.0%,灵敏度=88.5%,特异度=70.8%)。结论两种亚型患者额脑白质微观结构异常既存在共性也存在异质性。颞叶矢状层和胼胝体的白质损害可能是ADHD疾病本身的病理生理基础,而额叶区域的异常改变或为不同亚型患者间的区分点。展开更多
文摘Background: The aim of this study was to evaluate the feasibility of a dualbolus protocol, where a first bolus of an intravascular tracer is used to measure perfusion, followed by a second bolus of a freely filtered gadolinium-containing agent to measure filtration capacity. Methods: The study was conducted in mice subjected to complete unilateral ureteral obstruction (UUO), and sham operated mice were used as controls. Dynamic contrast- en-hanced MRI was performed 2 days after surgery. Results and discussions: Mean signal-time curves of the renal cortex, renal medulla and abdominal aorta were used to calculate the relative renal blood flow (rRBF), relative renal blood volume (rRBV), mean transit time (MTT) and the glomerular transfer rate Ktrans. We demonstrated that kidneys suffering from two days of UUO showed a decrease in cortical as well as medullary rRBF compared to kidneys from sham-operated mice. Further, we found no changes in rRBV and MTT among groups, neither in the cortex nor in the medulla. The renal functional parameter Ktrans showed a tendency (but statistically insignificant) to be reduced in the ob-structed kidney compared to the sham-operated mice. Conclusions: We showed our first experiences with the consecutive use of intra- and extra-vascularly distributed agents in a renal-diseased mouse model, allowing analysis of both functional haemo- dyamics and filtration capacity in kidneys.
文摘目的 利用MRI影像数据,基于亚型与阶段推断算法(SuStaIn)构建精神分裂症(SCZ)与双相情感障碍(BD)跨诊断的脑萎缩进展亚型框架。方法 纳入190例SCZ与BD患者,以及158名健康对照组。基于其T1WI MRI影像,提取17个感兴趣脑区的灰质体积(GMV),利用SuStaIn进行亚型与分期建模。利用方差分析评估亚型间临床特征差异,Spearman分析验证临床特征差异及其与模型分期的相关性。结果 SuStaIn模型识别出两类不同的大脑萎缩进展轨迹:小脑主导型(以小脑起始,逐步累及布洛卡区、额叶与岛叶)与前额叶主导型(以额叶起始,扩展至扣带回、颞叶)。前额叶主导型患者在阳性症状评分上显著高于小脑主导型(14.2±5.4 vs. 9.15±4.1,P=0.029)。亚组分析表明:前额叶主导型患者表现出更严重的阳性症状(BD:14.4±5.2 vs. 11.3±4.5,P=0.041;SCZ:8.6±2.8 vs. 7.2±1.7,P=0.038)。两种亚型的小脑(r=-0.169,P=0.007)和前额叶(r=-0.193,P=0.002)GMV随分期推移均呈下降趋势,阳性症状(r=0.331,P=0.012)、阴性症状(r=0.283,P=0.033)及一般症状(r=0.411,P=0.002)的症状严重程度增加。结论基于横断面MRI数据,发现SCZ与BD的两类跨诊断脑萎缩路径,且随分期推移,临床症状加重。结果支持精神障碍为一种具有明确空间-时间进展特征的神经退行性过程。
文摘目的探索不同亚型注意缺陷多动障碍(attention-deficit/hyperactivity disorder,ADHD)患者脑白质微观结构异常并建立分类模型。方法前瞻性纳入2019年1月-2021年9月就诊于四川大学华西医院的ADHD患者及经广告招募的健康对照者,所有受试者均接受弥散张量成像扫描。通过全脑基于体素的分析对混合型ADHD(combined subtype of ADHD,ADHD-C)、注意缺陷型ADHD(inattentive subtype of ADHD,ADHD-I)和对照组的各向异性分数(fractional anisotropy,FA)参数图进行组间比较。运用支持向量机分类器及特征选择方法构建个体化ADHD分类模型,并对3组受试者两两之间的分类效能进行检测。结果共纳入26例ADHD-C型、24例ADHD-I型患者及26例健康对照者。3组受试者在双侧颞叶白质矢状层及胼胝体峡部FA值差异有统计学意义(P<0.005),前者表现为ADHD-C型患者<ADHD-I型患者<对照者,后者表现为ADHD-C型患者>ADHD-I型患者>对照者;两组亚型之间的差异点位于右侧额中回白质,表现为ADHD-C型>ADHD-I型。基于FA图的分类模型在对两种亚型患者间的分类预测中效能最高(P<0.05,总体准确率=76.0%,灵敏度=88.5%,特异度=70.8%)。结论两种亚型患者额脑白质微观结构异常既存在共性也存在异质性。颞叶矢状层和胼胝体的白质损害可能是ADHD疾病本身的病理生理基础,而额叶区域的异常改变或为不同亚型患者间的区分点。
文摘目的探讨甲苯噻嗪(xylazine,Xyl)通过抑制超极化激活环核苷酸门控阳离子通道(hyperpolarization-activated cyclic nucleotide-gated,HCN)电流产生镇痛作用的机制。方法对HCN亚型通道1(HCN1)基因敲除小鼠(HCN1-/-)及HCN1野生型小鼠(HCN1+/+)分别腹腔注射生理盐水及Xyl(10、20、30和40mg/kg),通过进行机械痛觉测试及甩尾试验方法检测Xyl的镇痛效果,计算出最大镇痛效应百分比(percent maximum possible effect,%MPE);HEK 293细胞转染HCN1质粒和HCN亚型通道2(HCN2)质粒,分为对照组及不同浓度Xyl(12.5、25、50和100μmol/L)实验组,利用全细胞膜片钳记录表达HCN1和HCN2离子通道的HEK 293细胞超极化激活电流(hyperpolarization-activated currents,Ih),计算Xyl对Ih的抑制率。结果HCN1+/+小鼠和HCN1-/-小鼠注射Xyl后对机械痛觉刺激和热辐射刺激反应的%MPE均为随着Xyl质量浓度增加而加大,当Xyl质量浓度为30mg/kg及40mg/kg时,HCN1-/-小鼠机械痛觉刺激测试的%MPE为(62.06±14.72)%和(69.92±16.09)%;甩尾试验%MPE为(52.50±1.97)%和(64.74±6.34)%。HCN1+/+小鼠机械痛觉刺激测试的%MPE为(75.47±8.06)%和(86.35±11.31)%;甩尾试验%MPE为(57.83±4.82)%和(74.98±9.35)%,等量Xyl对HCN1+/+小鼠与HCN1-/-小鼠的镇痛作用(机械痛觉刺激和甩尾试验)差异有统计学意义(P<0.05)。全细胞膜片钳试验结果显示,Xyl对HCN1及HCN2离子通道电流均产生了抑制作用,Xyl(12.5～100μmol/L)对HCN1的Ih的抑制率为(24.62±23.62)%～(62.40±15.48)%;HCN1的半数激活电压(V1/2)为:(-79.58±1.56)mV～(-98.95±3.57)mV。Xyl对HCN2的Ih的抑制率为(29.19±17.82)%～(80.02±6.64)%;HCN2的V1/2为:(-102.17±1.36)mV～(-117.48±2.38)mV。结论 Xyl对HCN1+/+小鼠的镇痛效果比HCN1-/-小鼠更好。Xyl可能是通过抑制HCN离子通道电流,从而产生镇痛作用。
