基于非小细胞肺癌双能CT表现及影像组学列线图模型预测其血管生成拟态

目的 基于非小细胞肺癌(NSCLC)双能CT (DECT)表现及影像组学构建联合列线图模型,分析其预测NSCLC血管生成拟态(VM)的价值。方法 回顾性分析137例经手术病理证实的单发NSCLC患者,以7 ∶ 3比例将其分为训练集和验证集。基于肺窗CT提取及筛选最优影像组学特征,计算影像组学评分。以单因素分析及多因素logistic回归分析筛选NSCLC表达VM的独立预测因素,分别以之构建临床、能谱及影像组学模型;基于独立预测因素构建联合列线图模型。采用受试者工作特征曲线评估各模型预测NSCLC VM的效能,以校准曲线分析模型的拟合度,以决策曲线分析评估模型的临床获益。结果 最终筛选出6个最优影像组学特征。病灶最大径、毛刺征、CT_{140 keV}及影像组学评分为NSCLC VM的独立预测因素(OR=2.25、9.69、0.99、-14.44,P均＜0.05)。临床、能谱及影像组学模型预测验证集NSCLC VM的曲线下面积(AUC)分别为0.83、0.85、0.87,均低于联合列线图模型(AUC=0.95,Z=2.14、2.10、2.07,P均＜0.05)。联合列线图模型预测结果与实际结果的一致性较好,且其临床获益较高。结论 基于DECT及影像组学构建的联合列线图模型能可有效预测NSCLC VM。     

基于T2WI影像组学模型产前预测胎盘植入性病变

目的 评估基于MR T2WI影像组学模型产前预测胎盘植入性病变（PAS）的价值。方法 回顾性分析241例孕妇及胎儿MRI,其中116例PAS、125例无PAS。按7：3比例将其分为训练集（n=168）和验证集（n=73）,于训练集提取并筛选半傅立叶采集单次激发快速自旋回波（HASTE）及真实稳态进动快速成像（TrueFISP）序列图像的影像组学特征,构建预测PAS的影像组学模型,并以回归分析方法构建临床模型、影像组学模型及临床-影像组学模型。采用校准曲线和受试者工作特征（ROC）曲线分析模型的效能,以决策曲线分析（DCA）评估其临床实用性。结果 对各序列图像分别提取1 130个影像组学特征,经LASSO回归等处理后,各筛选出9个影像组学特征,用于构建预测PAS的HASTE及TrueFISP影像组学模型。ROC曲线显示,临床模型、HASTE影像组学模型及TrueFISP影像组学模型在验证集中诊断PAS的曲线下面积（AUC）分别为0.882、0.968和0.930（P均>0.05）;HASTE联合TrueFISP影像组学模型的AUC为0.990,高于临床（Z=-2.36,P=0.02）、HASTE影像组学（Z=-2.48,P=0.02）及TrueFISP影像组学模型（Z=-2.43,P=0.02）;临床-HASTE-TrueFISP影像组学模型的AUC为0.995,与HASTE联合TrueFISP影像组学模型差异无统计学意义（Z=-0.85,P=0.40）,高于HASTE或TrueFISP影像组学模型（Z=-2.64、-2.47,P均<0.05）。临床模型之外,各模型在验证集数据中的校准度均较好;阈值取0~0.6时,其在验证集的临床净获益均大于临床模型。结论 基于产前HASTE及TrueFISP序列图像的联合影像组学模型有助于准确预测PAS。     

联合含瘤周肿瘤全体积CT影像组学特征及临床相关独立预测因子列线图预测肺腺癌淋巴血管侵犯

目的 观察基于含瘤周的肿瘤全体积(GPTV) CT影像组学特征及临床相关独立预测因子构建的联合模型列线图预测肺腺癌淋巴血管侵犯(LVI)的价值。方法 回顾性分析142例经病理证实的肺腺癌患者,以7 ∶ 3比例将其随机分为训练集(n=100,40例LVI阳性、60例LVI阴性)和验证集(n=42,17例LVI阳性、25例LVI阴性)。以单因素分析及多因素logistic回归分析筛选肺腺癌LVI的临床相关独立预测因子,以之构建临床模型。分别基于肿瘤全体积(GTV)及含瘤周3 mm、6 mm、9 mm的GPTV (GPTV₃、GPTV₆和GPTV₉)的增强动脉期CT图提取并筛选最佳影像组学特征,构建影像组学模型,即GTV、GPTV₃、GPTV₆和GPTV₉模型并筛选最佳者;基于后者的影像组学评分和临床相关独立预测因子构建联合模型,绘制列线图进行可视化。以受试者工作特征(ROC)曲线评估各模型预测肺腺癌LVI的效能,以决策曲线分析(DCA)评价联合模型列线图的价值。结果 性别、吸烟和毛刺征均为肺腺癌LVI的临床相关独立预测因子(P均＜0.05)。分别基于GTV、GPTV₃、GPTV₆及GPTV₉筛选出7、16、10及8个最佳影像组学特征,用于构建GTV、GPTV₃、GPTV₆及GPTV₉模型。GPTV₃模型预测训练集、验证集肺腺癌LVI的曲线下面积(AUC)分别为0.82、0.77,均高于GTV (0.79、0.72,Z=3.74、2.62,P均＜0.01)、GPTV₆(0.80、0.72,Z=2.40、2.06,P均＜0.05)及GPTV₉(0.77,0.72,Z=3.03、2.59,P均＜0.01),为最佳影像组学模型。联合模型列线图(0.86、0.73,Z=2.66、2.31,P均＜0.05)及GPTV₃模型(0.82、0.77,Z=2.23、2.54,P均＜0.05)于训练集和验证集的AUC均高于临床模型(0.73、0.61),而联合模型列线图与GPTV₃模型的AUC差异均无统计学意义(Z=1.57、0.88,P均＞0.05)。阈值取0.20~0.50时,联合模型列线图与GPTV₃模型的净获益相当,且均大于临床模型。结论 基于GPTV₃影像组学特征及临床相关独立预测因子的列线图可有效预测肺腺癌LVI。     

11C-蛋氨酸PET/CT影像组学模型评估胶质母细胞瘤异柠檬酸脱氢酶1状态

目的 观察¹¹C-蛋氨酸(MET)PET/CT影像组学模型评估胶质母细胞瘤异柠檬酸脱氢酶1(IDH1)状态的价值。方法 回顾性分析157例接受¹¹C-MET PET/CT检查的胶质母细胞瘤患者资料,包括68例IDH1突变及89例野生型;按8 ∶ 2比例将其分为训练集(n=125)与验证集(n=32)。基于PET/CT图像勾画病灶ROI并提取、筛选影像组学特征,分别建立逻辑回归(LR)、支持向量机(SVM)及决策树(DT)影像组学模型;同时基于患者年龄及影像组学特征绘制列线图;对比观察影像组学模型及临床-影像组学列线图评估IDH1状态的效能。结果 DT影像组学模型评估训练集胶质母细胞瘤IDH1状态的曲线下面积(AUC)为0.910,大于LR(0.697)及SVM(0.698)模型(P均＜0.05)。验证集中,DT模型评估胶质母细胞瘤IDH1状态的AUC为0.805,大于LR模型(0.740)及临床-影像组学列线图(0.704)(P均＜0.05)。结论 基于DT的¹¹C-MET PET/CT影像组学模型有助于评估胶质母细胞瘤IDH1状态。     

基于超声影像组学特征列线图模型术前鉴别早期与中晚期宫颈鳞癌

目的 观察基于经阴道超声影像组学特征建立的列线图模型术前鉴别早期与中晚期宫颈鳞癌的价值。方法 回顾性收集经术后病理证实的227例宫颈鳞癌患者,利用3D-Slicer软件于术前经阴道声像图中勾画ROI,提取并经冗余性分析、最小绝对收缩和选择算子(LASSO)和10折交叉验证筛选影像组学特征,构建影像组学模型并得到Radscore评分;利用多因素logistic回归纳入Radscore及临床资料构建列线图模型。比较2个模型术前鉴别早期与中晚期宫颈鳞癌的受试者工作特征曲线下面积(AUC);评估列线图模型的校准度及临床收益。结果 最终纳入18个超声影像组学特征;以之构建术前鉴别早期与中晚期宫颈鳞癌的影像组学模型在训练集和验证集的AUC分别为0.839和0.744;联合年龄、流产次数及Radscore评分构建的列线图模型在训练集和验证集的AUC分别为0.882和0.773。DeLong检验结果显示,上述2模型在训练集的AUC差异有统计学意义(P＜0.05)。Hosmer-Lemeshow检验显示,列线图模型在训练集和验证集的校准度均佳(χ²=5.053、7.063,P均＞0.05);决策曲线分析(DCA)显示其在0.01~1.00阈值区间净收益相对较大。结论 基于经阴道超声影像组学特征的列线图模型可于术前较好地鉴别早期与中晚期宫颈鳞癌。     

垂体相关临床及MRI影像组学特征联合列线图鉴别特发性中枢性性早熟与单纯乳房早发育

目的 观察垂体相关临床及MRI影像组学特征联合列线图鉴别特发性中枢性性早熟(ICPP)与单纯乳房早发育(PT)的价值。方法 纳入67例ICPP及51例PT共118例患儿,按照7 ∶ 3比例随机分为训练集(n=83)和验证集(n=35),记录其垂体相关临床资料,以多因素logistic回归分析筛选并建立临床模型。采集垂体MRI,基于矢状位T1WI提取垂体影像组学特征,以最大相关最小冗余、最小绝对收缩和选择算子及多因素logistic回归筛选最佳影像组学特征,构建影像组学模型。联合应用临床、MRI及影像组学特征构建列线图模型。绘制受试者工作特征曲线,评估模型鉴别诊断效能;以决策曲线分析(DCA)观察临床获益度。结果 训练集ICPP与PT患儿年龄、骨龄、体质量、黄体生成素(LH)基础值、卵泡刺激素基础值及垂体高度差异均有统计学意义(P均＜0.05)。骨龄及LH基础值是鉴别ICPP与PT的独立因素(OR=1.807、1.422,P均＜0.05),以之建立的临床模型鉴别训练集、验证集ICPP与PT的曲线下面积(AUC)分别为0.849和0.812。共提取垂体1 781个影像组学特征,于其中筛选出1个形态特征、1个一阶特征及1个灰度区域大小矩阵特征建立影像组学模型,其鉴别训练集和验证集ICPP与PT的AUC分别为0.956和0.947。基于最终得出的2个临床及3个垂体MRI影像组学特征构建的列线图模型鉴别训练集、验证集ICPP与PT的AUC分别为0.981、0.977,均优于临床模型(P均＜0.05),而与影像组学模型差异无统计学意义(P均＞0.05)。一定危险阈值范围内,列线图模型净收益最大。结论 基于垂体相关临床及MRI影像组学特征建立的联合列线图模型用于鉴别ICPP与PT具有较高价值。     

多时相CT影像组学模型预测胸腺瘤风险分类

目的 观察多时相CT影像组学模型预测胸腺瘤风险分类的价值。方法 纳入86例经病理确诊的单发胸腺瘤患者,包括32例高风险及54例低风险胸腺瘤,按照7∶3比例将其分为训练集(n=59)和验证集(n=27);采用单因素及多因素logistic回归分析训练集临床及CT特征,筛选胸腺瘤风险分类的独立预测因素,构建临床-CT模型。分别基于平扫、动脉期(AP)、静脉期(VP)、平扫+AP、平扫+VP、AP+VP及平扫+AP+VP提取并筛选最优影像组学特征,计算影像组学评分(Rad-score);采用受试者工作特征(ROC)曲线选取最佳影像组学模型,以之联合临床-CT特征构建联合模型。绘制ROC曲线,计算曲线下面积(AUC),评估各模型预测胸腺瘤风险分类的效能。结果 周围脂肪浸润是胸腺瘤风险分类的独立预测因素(OR=0.029,P=0.004)。ROC曲线显示,模型_AP+VP为最佳影像组学模型,其与联合模型预测训练集胸腺瘤风险分类的AUC分别为0.860及0.877,均高于临床-CT模型的0.736(Z=1.925、-2.464,P均＜0.05),预测验证集的AUC分别为0.835及0.847,亦高于临床-CT模型的0.641(Z=1.840、-2.137,P均＜0.05);模型_AP+VP与联合模型在训练集和验证集的AUC差异均无统计学意义(Z=-1.180、0.291,P均＞0.05)。结论 多时相CT影像组学模型可有效预测胸腺瘤风险分类。     

基于临床病理及常规和功能MRI影像组学模型预测乳腺癌腋窝淋巴结转移

目的 评估基于临床病理及常规和功能MRI（fMRI）影像组学模型预测乳腺癌腋窝淋巴结（ALN）转移的价值。方法 回顾性分析140例浸润性乳腺癌,按7∶3比例将其分为训练集（n=99）和验证集（n=41）。采用多因素Logistic回归分析分别建立基于临床病理及MRI特征的临床模型及各序列图像影像组学、联合序列影像组学以及临床病理及常规和fMRI影像组学的个体化模型,以受试者工作特征（ROC）曲线评价其诊断效能;比较个体化模型与临床模型曲线下面积（AUC）的差异,应用决策曲线分析（DCA）评估模型的临床获益。结果 临床模型预测训练集和验证集ALN转移的AUC分别为0.95和0.88;T2WI、DWI、DCE-MRI模型及联合序列模型在验证集中的AUC分别为0.67、0.71、0.72及0.76。个体化模型在训练集和验证集中的AUC为0.98和0.93,与临床模型差异均无统计学意义（Z=1.56、1.34,P=0.12、0.18）。DCA结果显示阈值>0.25时,个体化模型的净受益高于临床模型。结论 基于临床病理及常规和功能MRI的个体化模型预测乳腺癌ALN转移的效能与临床模型相当,其净受益高于后者,且均优于单一序列模型。     

增强动脉期CT影像组学特征联合临床术前预测胃癌脉管浸润

目的 观察增强动脉期CT影像组学特征联合临床术前预测胃癌脉管浸润(LVI)的价值。方法 回顾性纳入298例胃癌患者,根据是否伴LVI将其分为阳性组(n=155)及阴性组(n=143),并按7 ∶ 3比例分为训练集(n=208)及测试集(n=90)。基于增强动脉期CT图提取病灶影像组学特征,采用logistic回归分析筛选胃癌LVI的临床影响因素;分别采用支持向量机(SVM)、逻辑回归(LR)、随机森林(RF)及极端梯度提升树(XGBoost)建立影像组学模型、临床模型及临床-影像组学模型,评估各模型预测胃癌LVI的效能。结果 以SVM、LR、RF及XGBoost建立的影像组学模型预测训练集胃癌LVI的曲线下面积(AUC)分别为0.896、0.821、1.000及1.000,其在测试集的AUC分别为0.744、0.801、0.740及0.747。基于4种机器学习建立的临床模型在训练集的AUC均为0.810,在测试集均为0.840。基于SVM、LR、RF及XGBoost建立的临床-影像组学模型预测训练集胃癌LVI的AUC分别为0.920、0.900、1.000及1.000,其在测试集的AUC分别为0.900、0.890、0.840及0.790。测试集中,基于SVM、LR及RF的临床-影像组学模型的AUC均大于影像组学模型和临床模型(P均＜0.05)。结论 增强动脉期CT影像组学联合临床有助于术前预测胃癌LVI。     

基于MR-T2WI影像组学模型预测宫颈鳞癌临床分期

目的 观察基于MR-T2WI影像组学模型预测宫颈鳞癌临床分期的价值。方法 对159例经术后或活检病理证实的宫颈鳞癌患者采集盆部MRI,根据国际妇产科联盟（FIGO）分期系统及病理结果分为早期组（ⅠB~ⅡA期,n=73）和晚期组（ⅡB~Ⅳ期,n=86）。按照7 ：3比例将患者随机分为训练集（n=113）和验证集（n=46）。训练集包括52例早期、61例晚期宫颈鳞癌,验证集含21例早期及25例晚期宫颈鳞癌。提取轴位T2WI中病灶的影像组学特征,以最大相关最小冗余和最小绝对收缩选择算子回归分析方法筛选最优影像组学特征,构建预测早、晚期宫颈鳞癌的影像组学模型。分析影像组学模型的拟合优度,采用受试者工作特征（ROC）曲线评估模型的预测效能,以决策曲线分析（DCA）评估模型的临床应用价值。结果 共提取396个影像组学特征,最终筛选11个最优影像组学特征,并以之构建预测早、晚期宫颈鳞癌的影像组学模型。影像组学模型在训练集和验证集中的拟合优度均佳（χ²=2.68、8.87,P均>0.05）;其在训练集及验证集中的曲线下面积（AUC）均为0.80。DCA显示,阈值取0.10~1.00时,影像组学模型的净收益较大。结论 基于MR-T2WI的影像组学模型对预测宫颈鳞癌临床分期具有较高价值。     

Determination of creatine kinase isoenzyme MB activity in serum using immunological inhibition of creatine kinase M subunit activity. Activity kinetics and diagnostic significance in myocardial infarction.

This is a new method for the determination of creatine kinase isoenzyme MB activity in serum. The method uses direct activity measurement of creatine kinase B subunit activity after blocking of CK-M subunit activity by inhibiting antibodies. The test takes no longer than 15 min. The method yields an intra-serial C.V. of 2.0-12.9%, and a C.V. from day to day of 5.5%. The detection limit is 3.4 U/l creatine kinase MB. In the 95 cases with proven myocardial infarction several types of creatine kinase MB activity kinetics could be determined. The percentage of creatine kinase MB of peak CK-total is 6-25%, with a mean of 11.1%. The amount of creatine kinase MB with respect to total CK activity after reinfarction is higher than the amount after initial infarction.     

Dissociable correlates of two classes of retrieval processing in prefrontal cortex

Although substantial evidence suggests that the prefrontal cortex (PFC) implements processes that are critical for accurate episodic memory judgments, the specific roles of different PFC subregions remain unclear. Here, we used event-related functional magnetic resonance imaging to distinguish between prefrontal activity related to operations that (1) influence processing of retrieval cues based on current task demands, or (2) are involved in monitoring the outputs of retrieval. Fourteen participants studied auditory words spoken by a male or female speaker and completed memory tests in which the stimuli were unstudied foil words and studied words spoken by either the same speaker at study, or the alternate speaker. On "general" test trials, participants were to determine whether each word was studied, regardless of the voice of the speaker, whereas on "specific" test trials, participants were to additionally distinguish between studied words that were spoken in the same voice or a different voice at study. Thus, on specific test trials, participants were explicitly required to attend to voice information in order to evaluate each test item. Anterior (right BA 10), dorsolateral prefrontal (right BA 46), and inferior frontal (bilateral BA 47/12) regions were more active during specific than during general trials. Activation in anterior and dorsolateral PFC was enhanced during specific test trials even in response to unstudied items, suggesting that activation in these regions was related to the differential processing of retrieval cues in the two tasks. In contrast, differences between specific and general test trials in inferior frontal regions (bilateral BA 47/12) were seen only for studied items, suggesting a role for these regions in post-retrieval monitoring processes. Results from this study are consistent with the idea that different PFC subregions implement distinct, but complementary processes that collectively support accurate episodic memory judgments.     

俯卧位通气对高海拔地区肺复张治疗无效急性呼吸窘迫综合征患者氧合的影响

目的 探讨俯卧位通气对高海拔地区肺复张术(RM)治疗无效急性呼吸窘迫综合征(ARDS)患者的治疗作用.方法 从海拔2260m的地区医院筛选RM治疗无效的41例ARDS患者[平均氧合指数( PaO2/FiO2)较RM前升高＜20％视为RM无效],依不同病因分为肺内源性ARDS组(ARDSp组)和肺外源性ARDS组(ARDSexp组),每组再按信封法随机分为俯卧位组和仰卧位组,即ARDSp俯卧位组(11例)、ARDSp仰卧位组(9例)、ARDSexp俯卧位组(10例)、ARDSexp仰卧位组(11例).在通气前及通气1、2、3、4h监测动脉血氧分压( PaO2)、PaO2/FiO2、静态顺应性(Cst)、气道阻力(Raw)的变化.结果 通气lh时,ARDSexp俯卧位组PaO2/FiO2( mm Hg,l mm Hg=0.133 kPa)即较通气前显著升高(157.4±40.6比129.3±48.7,P＜0.05),并随通气时间延长呈持续增高趋势,4h达峰值(219.1 ±41.1);且ARDSexp俯卧位组通气3h内PaO2/FiO2较其他3组显著增高,另3组间则差异无统计学意义.ARDSp俯卧位组、ARDSexp俯卧位组通气4h时PaO2/FiO2均较相应仰卧位组显著增高(208.8±39.7比127.4±47.1,219.1±41.1比124.9±50.8,均P＜0.05).4组通气前后Cst无显著改变,各组间差异也无统计学意义.ARDSp俯卧位组通气4h时Raw(cmH2O·L-1·s-1)较通气前显著降低(6.8±1.7比10.7±1.8,P＜0.05),且明显低于其他3组;其他3组各时间点Raw组内及组间比较差异均无统计学意义.结论 俯卧位通气作为ARDS机械通气重要策略之一,可以改善RM无效高原ARDS患者的氧合,为抢救患者赢得宝贵的时间.     

Digital imaging among medical facilities

The Department of Veterans Affairs (VA) in the USA operates a network of 172 medical centres which all utilize a hospital information system (HIS) which has been developed and is currently maintained by the VA. During the past several years, an image management and communication module has been developed, installed and clinically utilized at the Washington DC and Maryland VA Medical Centres. This image management and communication system, referred to as the decentralized hospital computer program (DHCP) imaging system, is fully integrated with a commercial picture archiving and communication system (PACS). The system is utilized to capture, archive, and display all images generated within the hospital including radiology, nuclear medicine, pathology, endoscopy, bronchoscopy, and dermatology, intraoperative photographs, ECG data, and a limited number of paper documents. The ultimate goal of the project is to have all patient text and image data available at any clinical workstation to any authorized user anywhere within the network of medical centres. Clinical requirements for an imaging workstation include ease of use, rapid and reliable access to the complete set of patient information, and images which are of acceptable quality to meet the requirements of the user and the subspecialty. Patient confidentiality and data security must be safeguarded at all times. Integration of the images with the remainder of the patient's database was found to be critical to the success of the project. The experience at the Washington and Maryland facilities suggests that an imaging system that is successfully integrated with a hospital information system can provide substantial clinical and economic benefits both within and among medical centres. Clinical acceptance and utilization of the system has been excellent, particularly in diagnostic radiology where DHCP Imaging has been interfaced to a commercial PAC system. Based upon this initial experience, the VA has begun to deploy the system throughout its large network of medical centres.     

Myocardial elastography at both high temporal and spatial resolution for the detection of infarcts

Myocardial elastography is a novel method for noninvasively assessing regional myocardial function, with the advantages of high spatial and temporal resolution and high signal-to-noise ratio (SNR). In this paper, in-vivo experiments were performed in anesthetized normal and infarcted mice (one day after left anterior descending coronary artery [LAD] ligation) using a high-resolution (30 MHz) ultrasound system (Vevo 770, VisualSonics Inc., Toronto, ON, Canada). Radiofrequency (RF) signals of the left ventricle (LV) in longitudinal (long-axis) view and the associated electrocardiogram (ECG) were simultaneously acquired. Using a retrospective ECG gating technique, 2-D full field-of-view RF frames were acquired at an extremely high frame rate (8 kHz) that resulted in high-quality incremental displacement and strain estimation of the myocardium. The incremental results were further accumulated to obtain the cumulative displacements and strains. Two-dimensional and M-mode displacement images and strain images (elastograms), as well as displacement and strain profiles as a function of time, were compared between normal and infarcted mice. Incremental results clearly depicted cardiac events including LV contraction, LV relaxation and isovolumetric phases in both normal and infarcted mice, and also evidently indicated reduced motion and deformation in the infarcted myocardium. The elastograms indicated that the infarcted regions underwent thinning during systole rather than thickening, as in the normal case. The cumulative elastograms were found to have higher elastographic SNR (SNR(e)) than the incremental elastograms (e.g., 10.6 vs. 4.7 in a normal myocardium, and 6.0 vs. 2.4 in an infarcted myocardium). Finally, preliminary statistical results from nine normal (m = 9) and seven infarcted (n = 7) mice indicated the capability of the cumulative strain in differentiating infracted from normal myocardia. In conclusion, myocardial elastography could provide regional strain information at simultaneously high temporal (>/=0.125 ms) and spatial ( approximately 55 microm) resolution as well as high precision ( approximately 0.05 microm displacement). This technique was thus capable of accurately characterizing normal myocardial function throughout an entire cardiac cycle, at the same high resolution, and detecting and localizing myocardial infarction in vivo.     

Clinical Pharmacokinetics of Morphine

Morphine, the most widely used mu-opioid analgesic for acute and chronic pain, is the standard against which new analgesics are measured. A thorough understanding of the pharmacokinetics of morphine is required in order to safely and effectively use this analgesic in a wide variety of patients with different levels of organ function. A MEDLINE search was conducted to identify literature published between 1966 and January 2002 relevant to the pharmacokinetics of morphine. These publications were reviewed and the literature summarized regarding unique and clinically important elements of morphine disposition relative to its parenteral administration (including intravenous, intramuscular, subcutaneous, epidural and intrathecal administration), absorption profile (immediate release, controlled release, and sublingual/buccal, and rectal administration), distribution, and its metabolism/ excretion. Special populations, including infants, elderly, and those with renal/liver failure, have a unique morphine pharmacokinetic profile that must be taken into account in order to maximize analgesic efficacy and reduce the risk of adverse events.