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。     

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。     

瘤内及瘤周表观弥散系数影像组学特征预测髓母细胞瘤患儿预后

目的 观察瘤内及瘤周表观弥散系数（ADC）影像组学特征预测髓母细胞瘤（MB）患儿预后的价值。方法 回顾性分析74例MB患儿资料,根据术后2年随访结果将其分为进展组（n=29）及无进展组（n=45）,并按6：4比例分为训练集（n=44）或验证集（n=30）。基于ADC图提取并筛选瘤内及瘤周影像组学特征,分别建立瘤内、瘤周及瘤内+瘤周影像组学模型,并以之结合临床及常规影像学特征建立联合模型;比较各模型预测MB患儿预后的效能。结果 训练集中,临床-常规影像-瘤周影像组学模型、临床-常规影像-瘤内+瘤周影像组学模型曲线下面积（AUC）均大于单一瘤周影像组学模型（P均<0.05）;验证集中,临床-常规影像学-瘤内+瘤周影像组学模型的AUC最大,但与其他模型差异均无统计学意义（P均>0.05）。结论 瘤内及瘤周ADC影像组学特征可用于预测MB患儿预后;联合临床及常规影像学特征或有助于提高预测效能。     

增强CT联合直方图分析鉴别诊断腮腺Warthin瘤与多形性腺瘤

目的 观察增强CT联合直方图分析鉴别诊断腮腺Warthin瘤与多形性腺瘤（PA）的价值。方法 对37例Warthin瘤（Warthin瘤组）及28例PA（PA组）行颌面部CT平扫及增强检查，测量平扫及增强CT动脉期（AP）及静脉期（VP）病灶CT值，记录其强化方式及双期增强净强化值，计算增强CT相关直方图参数，包括均值（Mean）、标准差（StdDev）、最小值（Min）、最大值（Max）、中位数（Median）、偏度（Skew）及峰度（Kurt）。比较组间各参数值差异，绘制各参数鉴别诊断腮腺Warthin瘤与PA的ROC曲线，分析其诊断效能。结果 组间各期CT值、AP净强化值及强化方式差异均有统计学意义（P均<0.05），Mean_AP、Min_AP、Max_AP、Median_AP、Skew_AP、Mean_VP、StdDev_VP、Min_VP、Median_VP及Skew_VP差异均有统计学意义（P均<0.05）。强化方式、AP净强化值、Mean_AP、Min_AP、Max_AP、Median_AP及Skew_AP鉴别诊断PA与Warthin瘤的AUC及约登指数均高于VP直方图参数，其中Skew_AP的约登指数最高（0.71），AUC为0.88；强化方式+Skew_AP联合诊断效能最高，其AUC、约登指数、敏感度及特异度分别为0.94、0.80、83.58%及96.43%。结论 增强CT联合AP直方图分析有助于鉴别腮腺Warthin瘤与多形性腺瘤，各参数联合诊断效能优于单一参数。     

瘤内与瘤周CT影像组学模型结合临床及常规CT特征鉴别肺原位腺癌与微浸润性腺癌

目的 观察基于平扫CT瘤内及瘤周影像组学模型联合临床及常规CT特征鉴别肺原位腺癌(AIS)与微浸润性腺癌(MIA)的价值。方法 回顾性分析180例孤立性AIS及180例孤立性MIA肺结节患者,随机将其中各160例纳入训练集(n=320)、各20例纳入测试集(n=40)。以训练集AIS与MIA间差异有统计学意义的临床及常规CT特征构建临床模型;勾画瘤内(CTi)及包含瘤周2 mm(CTi+p2mm)、4 mm(CTi+p4mm)ROI,提取并筛选其影像组学特征,分别以之构建CTi模型、CTi+p2mm模型及CTi+p4mm模型;绘制受试者工作特征(ROC)曲线,计算曲线下面积(AUC),评价各模型效能,遴选预测测试集MIA效能最佳者,联合临床及常规CT特征构建联合模型,观察临床模型、最佳影像组学模型及联合模型的AUC、校准度及净收益。结果 训练集内,相比AIS,MIA结节直径较大、密度不均匀、伴血管穿行结节占比较高(P均＜0.05)。CTi+p2mm模型鉴别测试集MIA与AIS效能最高(AUC=0.838,P＜0.05);以之结合临床及常规CT特征构建的联合模型鉴别诊断效能更佳(AUC=0.867,P＜0.05)。联合模型的校准度及0.60~0.90阈值概率区间的临床净收益较高。结论 基于平扫CT构建的瘤内和瘤周2 mm ROI影像组学模型能有效鉴别肺MIA与AIS,联合临床及常规CT特征可进一步提高模型鉴别效能。     

增强CT模型及影像组学模型预测肾透明细胞癌WHO/ISUP分级

目的 比较增强CT模型与影像组学模型预测肾透明细胞癌（ccRCC）WHO/ISUP分级的效能。方法 回顾性分析131例经病理确诊ccRCC患者,按照3 ∶ 2比例分层抽样分为训练集（n=78）和验证集（n=53）。根据2016版肾癌WHO/ISUP病理分级标准,以Ⅰ~Ⅱ级为低级别、Ⅲ~Ⅳ级为高级别ccRCC。训练集55例低级别、23例高级别ccRCC;验证集37例低级别、16例高级别ccRCC。以训练集构建增强CT模型及影像组学模型预测ccRCC级别,于验证集加以验证,比较其诊断效能。结果 增强CT模型在训练集及验证集预测高、低级别ccRCC的曲线下面积（AUC）分别为0.89及0.76,敏感度分别0.83及0.56,特异度分别为0.84及0.87;影像组学模型的AUC分别为0.98及0.85,敏感度分别0.96及0.91,特异度分别为0.75及0.84。训练集中影像组学模型的AUC大于增强CT模型（Z＝2.05,P<0.05）,验证集中二者AUC差异无统计学意义（Z＝0.95,P=0.34）。决策曲线分析结果显示高风险概率阈值为0.08~1.00时,影像组学模型净获益高于增强CT模型。结论 影像组学模型预测ccRCC WHO/ISUP分级的效能优于增强CT模型。     

平扫及钆塞酸二钠增强MRI鉴别诊断透明细胞型与普通型肝细胞癌

目的 探讨平扫及钆塞酸二钠（Gd-EOB-DTPA）增强MRI对鉴别诊断透明细胞型肝细胞癌（CCHCC）与普通型肝细胞癌（NOS-HCC）的价值。方法 纳入经手术病理证实的36例CCHCC（CCHCC组）和72例年龄匹配的NOS-HCC患者（NOS-HCC组）,以单因素及分析多因素logistic回归分析回顾性评估其临床、病理及上腹部平扫+Gd-EOB-DTPA增强MRI,筛选鉴别CCHCC与NOS-HCC的独立预测因素;绘制受试者工作特征（ROC）曲线,计算曲线下面积（AUC）,评价MRI相关独立预测因素及其联合鉴别CCHCC与NOS-HCC的效能。结果 病理Edmondson-Steiner分级及MRI见病灶含脂肪成分、平扫T1WI病灶与肝脏信号强度比值（LLR_T1WI）及病灶与肌肉信号强度比值（LMR_T1WI）均为CCHCC与NOS-HCC的独立预测因素（P均<0.05）。以病灶含脂肪成分及LLR_T1WI、LMR_T1WI鉴别CCHCC与NOS-HCC的AUC分别为0.652、0.689、0.687,三者联合的AUC为0.762,高于单一病灶内含脂肪成分（Z=-2.401,P=0.016）,而与单一LLR_T1WI（Z=-1.841,P=0.066）及LMR_T1WI（Z=-1.440,P=0.150）差异均无统计学意义。结论 平扫及Gd-EOB-DTPA增强MRI可用于鉴别CCHCC与NOS-HCC。     

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。     

基于增强CT影像组学术前预测胃腺癌淋巴结转移

目的 观察增强CT影像组学模型术前预测胃腺癌淋巴结转移（LNM）的价值。方法 回顾性分析193例经术后病理证实的单发胃腺癌的腹部双期增强CT资料,将其分为训练集（n=97）和验证集（n=96）,比较LNM （+）与LNM （－）肿瘤CT表现的差异。分别于增强动脉期和静脉期CT提取病灶影像组学特征,构建相应影像组学标签;将单因素分析有统计学意义的CT参数及其影像组学标签纳入多因素logistic回归分析,筛选胃腺癌LNM的独立预测因素,分别建立临床模型及影像组学列线图。采用受试者工作特征（ROC）曲线评估各模型预测胃腺癌LNM的效能,计算曲线下面积（AUC）,比较其差异。结果 训练集含54例LNM （+）和43例LNM （－）,验证集含58例LNM （+）和38例LNM （－）。LNM （+）患者肿瘤厚度和阳性淋巴结占比均高于LNM （－）者（P均<0.05）。肿瘤厚度及淋巴结状态均为LNM的独立预测因素（P均<0.01）并用于构建临床模型。淋巴结状态和静脉期影像组学标签是胃腺癌LNM的独立预测因素（P均<0.01）,以之构建的影像组学列线图在训练集和验证集中的AUC分别为0.810和0.778,与临床模型AUC差异均无统计学意义（0.772、0.762,Z=1.11、0.27,P=0.27、0.78）。结论 基于增强CT影像组学模型术前预测胃腺癌LNM效能较佳。     

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。     

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.