A multivessel model describing replenishment kinetics of ultrasound contrast agent for quantification of tissue perfusion

To improve the quantification of tissue perfusion using intermittent sonography, a new model describing replenishment kinetics of microbubbles is proposed. The new approach takes into account the variability of blood flow velocities found in vivo, especially in tumors, and consistently describes the refilling process of microbubbles. Based upon this model, blood volume, blood velocity, blood flow and perfusion in 17 experimental tumors were calculated, and compared with the results obtained with the established, phenomenologically derived exponential kinetic model. In contrast to the existing model, our approach describes tissue vascularization more physiologically and allows deduction of a consistent new hyperbolic model for quantification of intermittent sonography. Blood volume and mean blood velocity did significantly correlate between both the new and the established model (k=0.99; k=0.94, both p<0.001). However, mean tumor blood velocity was lower (-19%, p<0.01) with the established model compared to the newly developed model. In addition, the range and distribution of blood flow velocities found in vivo can be estimated with the new model. Furthermore, it uses simpler mathematical fitting routines and allows easier data acquisition, which may allow a more practicable clinical application of intermittent sonography. In conclusion, a more valid, detailed and accurate calculation of perfusion parameters, especially of tumors, can be derived in vivo with the new multivessel model of intermittent sonography.     

Hierarchical Bayesian myocardial perfusion quantification

Myocardial blood flow can be quantified from dynamic contrast-enhanced magnetic resonance (MR) images through the fitting of tracer-kinetic models to the observed imaging data. The use of multi-compartment exchange models is desirable as they are physiologically motivated and resolve directly for both blood flow and microvascular function. However, the parameter estimates obtained with such models can be unreliable. This is due to the complexity of the models relative to the observed data which is limited by the low signal-to-noise ratio, the temporal resolution, the length of the acquisitions and other complex imaging artefacts.In this work, a Bayesian inference scheme is proposed which allows the reliable estimation of the parameters of the two-compartment exchange model from myocardial perfusion MR data. The Bayesian scheme allows the incorporation of prior knowledge on the physiological ranges of the model parameters and facilitates the use of the additional information that neighbouring voxels are likely to have similar kinetic parameter values. Hierarchical priors are used to avoid making a priori assumptions on the health of the patients. We provide both a theoretical introduction to Bayesian inference for tracer-kinetic modelling and specific implementation details for this application.This approach is validated in both in silico and in vivo settings. In silico, there was a significant reduction in mean-squared error with the ground-truth parameters using Bayesian inference as compared to using the standard non-linear least squares fitting. When applied to patient data the Bayesian inference scheme returns parameter values that are in-line with those previously reported in the literature, as well as giving parameter maps that match the independant clinical diagnosis of those patients.     

Direct comparison of stress- and rest-dual-energy computed tomography for detection of myocardial perfusion defect

We assessed the diagnostic performance of stress- and rest-dual-energy computed tomography (DECT) and their incremental value when used with coronary CT angiography (CCTA) compared with combined invasive coronary angiography (ICA)/cardiovascular magnetic resonance (CMR) for detecting hemodynamically significant stenosis causing a myocardial perfusion defect. Forty patients (30 men; mean age, 63.4 ± 8.8 years) with known or suspected coronary artery disease detected by CCTA underwent stress- and rest-DECT, CMR, and ICA. DECT iodine maps were compared with CMR on a per-segment and per-vessel basis. Diagnostic value of CCTA was assessed on a per-vessel basis before and after stress- and rest-DECT and compared to that of ICA/CMR. Compared to CMR, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of rest-DECT for detecting segment (vessel)-based perfusion defects were 29 % (46 %), 88 % (79 %), 56 % (61 %), and 70 % (67 %), respectively. Corresponding values using stress-DECT were 73 % (94 %), 83 % (74 %), 70 % (72 %), and 85 % (95 %), respectively. There was fair (κ = 0.39) agreement between rest- and stress-DECT iodine maps in identifying segments with perfusion defects. Compared with the ICA/CMR for identifying hemodynamically significant stenoses, per-vessel territory sensitivity, specificity, PPV, and NPV of CCTA were 91, 56, 55, and 91 %, respectively; those using CCTA/rest-DECT were 42, 83, 59, and 70 %, respectively; and those using CCTA/stress-DECT were 87, 79, 71, and 91 %, respectively. The area under the receiver operating characteristic curve decreased from 0.74 to 0.62 (P = 0.06) using CCTA/rest-DECT but increased to 0.83 (P = 0.02) using CCTA/stress-DECT. Stress-DECT has incremental value when used with CCTA for detecting hemodynamically significant stenoses.     

Physics-informed neural networks for myocardial perfusion MRI quantification

Tracer-kinetic models allow for the quantification of kinetic parameters such as blood flow from dynamic contrast-enhanced magnetic resonance (MR) images. Fitting the observed data with multi-compartment exchange models is desirable, as they are physiologically plausible and resolve directly for blood flow and microvascular function. However, the reliability of model fitting is limited by the low signal-to-noise ratio, temporal resolution, and acquisition length. This may result in inaccurate parameter estimates.This study introduces physics-informed neural networks (PINNs) as a means to perform myocardial perfusion MR quantification, which provides a versatile scheme for the inference of kinetic parameters. These neural networks can be trained to fit the observed perfusion MR data while respecting the underlying physical conservation laws described by a multi-compartment exchange model. Here, we provide a framework for the implementation of PINNs in myocardial perfusion MR.The approach is validated both in silico and in vivo. In the in silico study, an overall decrease in mean-squared error with the ground-truth parameters was observed compared to a standard non-linear least squares fitting approach. The in vivo study demonstrates that the method produces parameter values comparable to those previously found in literature, as well as providing parameter maps which match the clinical diagnosis of patients.     

A comparison of video and digital data in the assessment of myocardial perfusion abnormalities by myocardial contrast echocardiography

Objective: The objective of the present study was to compare the digital and video data of myocardial contrast echocardiography (MCE) to assess altered myocardial blood flow produced by graded coronary stenoses. Methods: Three grades of left anterior descending (LAD) coronary artery stenosis and occlusion were created in eight open-chest canine models. MCE was performed with BR1 infusion by harmonic power Doppler with ECG gated intermittent triggered imaging at pulsing intervals ranging from 1:1 to 1:10. For images that were recorded simultaneously on both a videotape (video data) and an optical disk (digital data), myocardial signal intensity in the LAD region was plotted vs. pulsing intervals and was fitted to an exponential function:y=A(1 − e^−bt ), where A is the peak plateau signal intensity, and b is the rate of signal intensity rise for quantification of myocardial blood flow. Results: Both values for A and b progressively decreased with a greater level of stenosis. The correlation of A with myocardial blood flow (determined by use of fluorescent microspheres) was weak with digital data (r= 0.38, p= 0.037), and was insignificant with video data (r= 0.16, p= 0.38). The correlation of b with microsphere-derived myocardial blood flow was better than that of A with both video and digital data, and was similar between the two kinds of data (video:r= 0.69, p < 0.0001; digital:r= 0.68, p < 0.0001). Conclusions: Video and digital MCE data are equivalent in their ability to quantify altered myocardial blood flow produced by graded coronary stenoses.     

实时心肌超声造影评估心肌灌注的临床研究

目的探讨冠状动脉支架置入术前后局部心肌血流灌注的变化。方法对7例正常人和20例冠心病患者支架术前后,分别行实时心肌超声造影检查,根据造影剂的充盈程度进行评分,并观察双嘧达莫负荷前后闪烁显像时,心肌血流再灌注状况。结果治疗前缺血心肌的造影记分指数负荷前后均低于正常心肌,支架术后灌注明显改善,基础状态和负荷后的造影记分、记分指数较术前好转。结论冠状动脉支架置入术可改善缺血心肌血流灌注,实时心肌超声造影可评价心肌微循环灌注。     

Method for the quantitation of myocardial perfusion during myocardial contrast two-dimensional echocardiography

This article describes the hardware and software components of two systems designed for quantitative analysis of data obtained during myocardial contrast two-dimensional echocardiography. One system is meant for off-line analysis of data, whereas the other is designed for on-line analysis, especially in the operating room. The algorithms used for data transfer, selection of appropriate frames, data alignment, derivation of time-intensity plots, and curve-fitting and parameter generation are described in some detail. It is hoped that this information will be of use to others who work in the field of myocardial perfusion imaging.     

Single breath-hold assessment of cardiac function using an accelerated 3D single breath-hold acquisition technique - comparison of an intravascular and extravascular contrast agent

Background

Cardiovascular magnetic resonance (CMR) is the current gold standard for the assessment of left ventricular (LV) function. Repeated breath-holds are needed for standard multi-slice 2D cine steady-state free precession sequences (M2D-SSFP). Accelerated single breath-hold techniques suffer from low contrast between blood pool and myocardium. In this study an intravascular contrast agent was prospectively compared to an extravascular contrast agent for the assessment of LV function using a single-breath-hold 3D-whole-heart cine SSFP sequence (3D-SSFP).

Methods

LV function was assessed in fourteen patients on a 1.5 T MR-scanner (Philips Healthcare) using 32-channel coil technology. Patients were investigated twice using a 3D-SSFP sequence (acquisition time 18–25 s) after Gadopentetate dimeglumine (GdD, day 1) and Gadofosveset trisodium (GdT, day 2) administration. Image acquisition was accelerated using sensitivity encoding in both phase encoding directions (4xSENSE). CNR and BMC were both measured between blood and myocardium. The CNR incorporated noise measurements, while the BMC represented the coeffiancy between the signal from blood and myocardium [1]. Contrast to noise ratio (CNR), blood to myocardium contrast (BMC), image quality, LV functional parameters and intra-/interobserver variability were compared. A M2D-SSFP sequence was used as a reference standard on both days.

Results

All 3D-SSFP sequences were successfully acquired within one breath-hold after GdD and GdT administration. CNR and BMC were significantly (p < 0.05) higher using GdT compared to GdD, resulting in an improved endocardial definition. Using 3D-SSFP with GdT, Bland–Altman plots showed a smaller bias (95% confidence interval LVEF: 9.0 vs. 23.7) and regression analysis showed a stronger correlation to the reference standard (R² = 0.92 vs. R² = 0.71), compared to 3D-SSFP with GdD.

Conclusions

A single-breath-hold 3D-whole-heart cine SSFP sequence in combination with 32-channel technology and an intravascular contrast agent allows for the accurate and fast assessment of LV function.

Trial registration

The study was approved by the local research ethics committee (Study No. 07/Q0704/2) and was registered with the Medicines and Healthcare Products Regulatory Agency (MHRA Study No. 28482/0002/001–0001, EudraCTnumber 2006–007042).     

超声造影剂对犬缺血再灌注心肌的靶向显像及其机制研究

目的用自制的靶向超声造影剂实现无创性地评价犬心肌缺血再灌注,同时研究其靶向性作用机制。方法将自行研制的表面活性剂超声造影剂“表活显”(surfactantfluorocarbon-filledmicrobubbles,SFCMB)与磷脂酰丝氨酸(phosphatidylserine,PS)结合,制备成靶向超声造影剂(SFCMB-PS),在实时心肌超声造影(MCE)条件下,用SFCMB-PS对犬心肌缺血再灌注模型进行延迟心肌显像。流式细胞术测定白细胞激活前和激活后与SFCMB-PS的结合情况以及在补体和β2整合素中的Mac-1缺乏时激活的白细胞与SFCMB-PS的结合情况。结果延迟心肌显像表明缺血再灌注区的造影剂回声较正常区的回声明显增强。流式细胞术证明了PS结合在造影剂微泡的表面,未激活的白细胞与微泡的结合率为(5.27±0.75)%,激活的白细胞与微泡的结合率为(39.67±6.83)%,结合率明显提高(P<0.01);补体和β2整合素中的Mac-1缺乏时,两者的结合明显受到抑制,结合率降到(12.27±1.66)%(P<0.01)和(10.90±2.40)%(P<0.01)。结论SFCMB-PS可以无创性地评价缺血再灌注损伤心肌的部位及其严重程度。SFCMB-PS是通过β2整合素中的Mac-1和补体介导途径与激活的白细胞结合并进入细胞内的。     

Dose response of the intravascular contrast agent gadofosveset trisodium in MR perfusion imaging of the myocardium using a quantitative evaluation

This study was performed to determine the best concentration of gadofosveset at 1.5 and 3 T MRI for quantitative myocardial perfusion analysis. 18 healthy volunteers have been examined at a 1.5 and a 3 T MRI system assigned to one of three dose groups: low dose (0.00375 mmol/kg), medium dose (0.0075 mmol/kg), high dose (0.0150 mmol/kg). A T1-weighted saturation recovery turboFLASH sequence with parallel imaging was used. Two perfusion scans were performed for each field strength and volunteer. Peak signal-to-noise-ratio, maximum contrast-enhancement-ratio and myocardial blood flow (MBF) were calculated. MBF values were significantly higher at 1.5 T in the medium and the high dose groups than in the low dose group (p < 0.001). Higher MBF values could be found at 3 T for the second perfusion scan in the medium and both perfusion scans in the high dose group compared to the low dose group. Optimal dose of gadofosveset for quantitative perfusion analysis at 1.5 T is 0.00375 mmol/kg as higher doses caused overestimation of the MBF. At 3 T 0.0075 mmol/kg seems to be the best dose for a single perfusion scan, while for a second perfusion scan MBF may be overestimated.     

左心声学造影对STEMI病人PCI术后心肌灌注及预后的评估价值

目的 探讨心肌声学造影(MCE)对急性STEMI病人PCI术后评估心肌灌注及预后的价值。方法 纳入本院78例急性STEMI且行PCI手术患者的病例资料,且术后48h均行MCE,根据MCE结果分为A组(灌注充盈正常：心肌节段造影剂充盈均匀,完全显影)43例,B组(灌注充盈稀疏：心肌节段造影剂充盈不均匀或部分显影)20例,C组(灌注充盈缺损：心肌节段造影剂充盈缺损,完全不显影)15例。应用常规超声与MCE技术获取各组患者术后48h、1个月、3个月左心功能指标[左室射血分数(LVEF)、左心室舒张末期容积(LVEDV)、左心室收缩末期容积(LVESV)]。记录三组患者术后6个月、12个月、24个月的主要不良心血管事件(MACE)发生率,并应用Logistic向后逐步回归分析急性STEMI患者PCI术后发生MACE的独立危险因素。结果 与A组比较,B、C组LVEDV、LVESV均较高,Am、E、LVEF较低,差异均有统计学意义(均P＜0.05)。与B组比较,C组LVEDV、LVESV均较高,Am、E、LVEF较低,差异均有统计学意义(均P＜0.05)。与A组比较,B、C组PCI术后MACE发生率较高,差异均有统计学意义(均P＜0.05)。多因素Logistic回归分析结果显示,LVEDV、LVESV、LVEF、MCE结果均为影响急性STEMI患者PCI术后发生MACE的独立危险因素(P＜0.05)。结论 MCE可有效评估急性STEMI患者PCI术后心肌灌注情况,可独立预测术后MACE事件的发生,利于患者预后。     

Regional contrast agent quantification in a mouse model of myocardial infarction using 3D cardiac T1 mapping

Background

Quantitative relaxation time measurements by cardiovascular magnetic resonance (CMR) are of paramount importance in contrast-enhanced studies of experimental myocardial infarction. First, compared to qualitative measurements based on signal intensity changes, they are less sensitive to specific parameter choices, thereby allowing for better comparison between different studies or during longitudinal studies. Secondly, T₁ measurements may allow for quantification of local contrast agent concentrations. In this study, a recently developed 3D T₁ mapping technique was applied in a mouse model of myocardial infarction to measure differences in myocardial T₁ before and after injection of a liposomal contrast agent. This was then used to assess the concentration of accumulated contrast agent.

Materials and methods

Myocardial ischemia/reperfusion injury was induced in 8 mice by transient ligation of the LAD coronary artery. Baseline quantitative T₁ maps were made at day 1 after surgery, followed by injection of a Gd-based liposomal contrast agent. Five mice served as control group, which followed the same protocol without initial surgery. Twenty-four hours post-injection, a second T₁ measurement was performed. Local ΔR₁ values were compared with regional wall thickening determined by functional cine CMR and correlated to ex vivo Gd concentrations determined by ICP-MS.

Results

Compared to control values, pre-contrast T₁ of infarcted myocardium was slightly elevated, whereas T₁ of remote myocardium did not significantly differ. Twenty-four hours post-contrast injection, high ΔR₁ values were found in regions with low wall thickening values. However, compared to remote tissue (wall thickening > 45%), ΔR₁ was only significantly higher in severe infarcted tissue (wall thickening < 15%). A substantial correlation (r = 0.81) was found between CMR-based ΔR₁ values and Gd concentrations from ex vivo ICP-MS measurements. Furthermore, regression analysis revealed that the effective relaxivity of the liposomal contrast agent was only about half the value determined in vitro.

Conclusions

3D cardiac T₁ mapping by CMR can be used to monitor the accumulation of contrast agents in contrast-enhanced studies of murine myocardial infarction. The contrast agent relaxivity was decreased under in vivo conditions compared to in vitro measurements, which needs consideration when quantifying local contrast agent concentrations.     

实时心肌造影超声心动图对心肌灌注跨壁分布的实验研究

目的　探讨实时心肌造影超声心动图(MCE)评价心肌灌注跨壁分布的可行性。方法　健康 犬6只,建立冠状动脉前降支(LAD)分级狭窄动物模型,以超声血流计检测LAD血流量。采用低发射功 率的实时MCE技术和持续静脉注射造影剂(SonoVue)的方法,分别在基础、双嘧达莫诱发充血、LAD不同 程度狭窄、再灌注及完全结扎状态下进行MCE检查。分别将感兴趣区(ROI)置于心内膜层与心外膜层得 出信号强度 时间曲线,并与指数函数拟合得出A、β、A·β测值,进而计算出各项测值的跨壁梯度,即心 内 外膜层A比值(A EER)、心内 外膜层β比值(β EER)和心内 外膜层A·β比值(A·β EER)。结果 基础状态、充血状态及LAD血流量减少50%时,A、β以及A·β测值在心内、外膜层分布差异无显著性意 义(P>0.05),跨壁梯度接近1;LAD血流量减少75%时,心内膜层β与A·β测值明显低于心外膜层测 值,β EER、A·β EER降低(P均<0.01);减少90%时,心内、外膜层A、β及A·β均明显降低,但心内 膜层测值低于心外膜层测值,A EER、β EER、A·β EER明显降低(P均<0.01);再灌注10min后,A、β 及A·β测值恢复至基础水平(P>0.05),A EER、β EER、A·β EER接近1;完全结扎LAD90min后, 心内、外膜层各测值再次降低(P均<0.01)。结论　实时MCE技术可显示心肌灌注     

心肌声学造影评价急性心肌梗死患者心肌微循环的研究

目的 探讨心肌声学造影（MCE）评价急性心肌梗死（AMI）患者心肌微循环灌注的临床应用价值。方法 选择24例AMI患者,在冠状动脉造影前2d内,应用声诺维（SonoVue）经静脉注射,行间歇触发、二次谐波MCE检查,取左室短轴乳头肌水平切面,应用声学密度分析软件,定量各节段心肌声学密度的峰值强度（PI）、曲线下面积（AUC）;根据冠脉造影的结果,按冠脉直径狭窄程度（狭窄＜50％、50％≤狭窄＜70％、70％≤狭窄＜90％、狭窄≥90％）将其所供应的心肌节段的分为4组,分别进行组间声学密度参数的比较,并与冠脉的狭窄程度进行相关分析。结果 24例患者均顺利完成MCE检查。4组间的微循环灌注参数均存在显著差异（P＜0.05）,随冠脉狭窄程度的加重,其心肌微循环灌注参数（PI、AUC）指标降低越明显（P均＜0．01）,但其与冠脉狭窄程度均无明显相关性（P＞0．05）。结论 心肌声学造影可评价心肌微循环灌注,但其微循环灌注并非与冠脉狭窄程度完全一致。     

计算机辅助心肌超声造影定量评价心肌灌注的实验研究

目的 探讨计算机辅助心肌超声造影(MCE)定量评价心肌灌注的应用价值.方法 根据阻断和再灌注冠状动脉时间不同,将家兔分为两组:阻断30 min再灌注60 min(I组)和阻断120 min再灌注60 min(Ⅱ组).于冠状动脉阻断时和再灌注后行MCE,造影图像经自制计算机辅助软件处理后,自动得出每个节段的标化造影剂密度(CI),并对心肌灌注进行彩色编码.根据心肌灌注缺损(MPD)和异常的彩色编码区分别计算出危险心肌和梗死心肌面积,并分别与荧光微球染色和氯化三苯基四氮唑染色(TTC)结果对照分析.结果 再灌注后,I组和Ⅱ组的危险节段心肌CI值均较非危险节段减低(P＜0.01),标化后,仅Ⅱ组危险节段的标化C1值比非危险节段明显减低(P＜0.01),而I组危险节段的标化CI值与非危险节段间无明显差异.以标化CI为-70像素为截断值,识别梗死节段的敏感性为95%,特异性为87%.阻断冠状动脉时,MPD和异常彩色编码测量的危险心肌面积与荧光染色呈正相关(r=0.84,P=0.003和r=(0.91,P＜O.001);再灌注时,MPD和异常彩色编码测量的梗死心肌面积与TTC结果呈正相关(r=0.75,P＜0.001和r=0.89,P＜0.001).结论 计算机辅助MCE可以定量评估心肌灌注,识别危险和梗死心肌区域.     

The effect of ionic and nonionic x-ray contrast media on myocardial perfusion and myocardial function

The influence of injections of Amidotrizoate and Iopromide into the left coronary artery on global myocardial perfusion and function (pressures in the left ventricle, heart rate) as well as excitation formation and transmission was studied in 16 patients with ischaemic heart disease. No statistically significant differences in myocardial perfusion measured were found with xenon-133 in this small group between rest and dipyridamole load for ionic and non-ionic contrast media.     

Gd-DTPA作为肾脏CT血流灌注对比剂的动物实验研究

目的探讨Gd-DTPA作为肾脏CT增强对比剂用于肾脏血流灌注研究的可行性.方法 12只新西兰白兔,分组注射Gd-DTPA或碘对比剂,CT动态扫描获得主动脉和肾脏的时间-密度曲线,计算血流灌注数值.结果静脉注射0.5 mmol/(kg*ml) Gd-DTPA后,肾皮质增强(33.2±11.9) Hu.Gd-DTPA和碘对比剂获得的肾脏皮质、髓质血流灌注数值无明显差异.结论 Gd-DTPA能够作为X线对比剂用于肾脏增强CT检查,并用于研究肾脏血流灌注.     

应用实时心肌造影超声心动图对心肌灌注的定量评价

目的 确定实时心肌灌注显像技术定量评价左心室各节段心肌灌注的可行性。方法 应用实时显像技术对10条麻醉犬采集左室乳头肌中段短轴观图像。机械指数(MI)分别调至0．1，0．2和0．4，帧速设为20Hz，Optison分别以0．1，0.2和0．5ml／min的速度静脉滴注。在2～3次多普勒诱导微泡破裂后立即记录150帧实时图像。用肉眼和定量两种方法评价左室6节段的心肌浊化程度(前间隔、后间隔、下壁、后壁、侧壁和前壁)。以心肌信号强度对应实时图像制作曲线并拟合指数函数Y=A(1-e^-βt)。结果 采用低MI(MI为0．1或0．2)并以0．2或0．5ml／min的速度静脉滴注Optison的方法，实时显像技术可以获得充分的心肌浊化和清晰的左室心内膜轮廓，并能同时显示心肌增厚率和室壁运动。结论 实时心肌灌注显像技术不仅能够定量评价心肌灌注，而且可以同时评价心肌功能。     

Direct three-dimensional myocardial strain tensor quantification and tracking using zHARP

Images of myocardial strain can be used to diagnose heart disease, plan and monitor treatment, and to learn about cardiac structure and function. Three-dimensional (3D) strain is typically quantified using many magnetic resonance (MR) images obtained in two or three orthogonal planes. Problems with this approach include long scan times, image misregistration, and through-plane motion. This article presents a novel method for calculating cardiac 3D strain using a stack of two or more images acquired in only one orientation. The zHARP pulse sequence encodes in-plane motion using MR tagging and out-of-plane motion using phase encoding, and has been previously shown to be capable of computing 3D displacement within a single image plane. Here, data from two adjacent image planes are combined to yield a 3D strain tensor at each pixel; stacks of zHARP images can be used to derive stacked arrays of 3D strain tensors without imaging multiple orientations and without numerical interpolation. The performance and accuracy of the method is demonstrated in vitro on a phantom and in vivo in four healthy adult human subjects.