Arterial input function in a dedicated slice for cerebral perfusion measurements in humans

Object

We aimed to modify our previously published method for arterial input function measurements for evaluation of cerebral perfusion (dynamic susceptibility contrast MRI) such that it can be applied in humans in a clinical setting.

Materials and methods

Similarly to our previous work, a conventional measurement sequence for dynamic susceptibility contrast MRI is extended with an additional measurement slice at the neck. Measurement parameters at this slice were optimized for the blood signal (short echo time, background suppression, magnitude and phase images). Phase-based evaluation of the signal in the carotid arteries is used to obtain quantitative arterial input functions.

Results

In all pilot measurements, quantitative arterial input functions were obtained. The resulting absolute perfusion parameters agree well with literature values (gray and white matter mean values of 46 and 24 mL/100 g/min, respectively, for cerebral blood flow and 3.0% and 1.6%, respectively, for cerebral blood volume).

Conclusions

The proposed method has the potential to quantify arterial input functions in the carotid arteries from a direct measurement without any additional normalization.

     

A novel continuous arterial spin labeling approach for CBF measurement in rats with reduced labeling time and optimized signal-to-noise ratio efficiency

Objective  To develop a continuous arterial spin labeling (CASL) perfusion imaging method for cerebral blood flow (CBF) measurement in rats with reduced spin-labeling length and optimized signal-to-noise ratio (SNR _f ) per unit time. Materials and methods  In the proposed method, the longitudinal magnetization of brain tissue water in the imaging slice is prepared into a proper state before spin-labeling, and a post-tagging delay is employed after spin-labeling. The method was implemented on a 4.7 T small animal scanner. Numerical simulations and in vivo experiments were used to evaluate the performance of the method proposed. Results  With the proposed method, absolute CBF could be measured accurately from normal rat with a spin-labeling pulse as short as 400 ms, and yet employing the same formula as that used in the conventional CASL perfusion imaging method for calculation. The method also showed improved SNR _f per unit time over the conventional CASL perfusion imaging method and the pulsed arterial spin labeling perfusion imaging method FAIR. Conclusion  Compared to the conventional CASL perfusion imaging method, the proposed method would be advantageous for CBF measurement in small animals having short vascular transit time in terms of SNR _f per unit time and other benefits brought by shortened spin-labeling pulse.     

Effects of bolus injection duration on perfusion estimates in dynamic CT and dynamic susceptibility contrast MRI

Estimates of cerebral blood flow (CBF) and tissue mean transit time (MTT) have been shown to differ between dynamic CT perfusion (CTP) and dynamic susceptibility contrast MRI (DSC-MRI). This study investigates whether these discrepancies regarding CBF and MTT between CTP and DSC-MRI can be attributed to the different injection durations of these techniques. Five subjects were scanned using CTP and DSC-MRI. Region-wise estimates of CBF, MTT, and cerebral blood volume (CBV) were derived based on oscillatory index regularized singular value decomposition. A parametric model that reproduced the shape of measured time curves and characteristics of resulting perfusion parameter estimates was developed and used to simulate data with injection durations typical for CTP and DSC-MRI for a clinically relevant set of perfusion scenarios and noise levels. In simulations, estimates of CBF/MTT showed larger negative/positive bias and increasing variability for CTP when compared to DSC-MRI, especially for high CBF levels. While noise also affected estimates, at clinically relevant levels, the injection duration effect was larger. There are several methodological differences between CTP and DSC-MRI. The results of this study suggest that the injection duration is among those that can explain differences in estimates of CBF and MTT between these bolus tracking techniques.

     

Use of spin echo T2 BOLD in assessment of cerebral misery perfusion at 1.5 T

Inadequate blood supply relative to metabolic demand, a haemodynamic condition termed as misery perfusion, often occurs in conjunction with acute ischaemic stroke. Misery perfusion results in adaptive changes in cerebral physiology including increased cerebral blood volume (CBV) and oxygen extraction ratio (OER) to secure substrate supply for the brain. It has been suggested that the presence of misery perfusion may be an indication of reversible ischaemia, thus detection of this condition may have clinical impact in acute stroke imaging. The ability of single spin echo T₂ to detect misery perfusion in the rat brain at 1.5 T owing to its sensitivity to blood oxygenation level dependent (BOLD) contrast was studied both theoretically and experimentally. Based on the known physiology of misery perfusion, tissue morphometry and blood relaxation data, T₂ behaviour in misery perfusion was simulated. The interpretation of these computations was experimentally assessed by quantifying T₂ in a rat model for cerebral misery perfusion. CBF was quantified with the H₂ clearance method. A drop of CBF from 58 ± 8 to 17 ± 3 ml/100 g min in the parieto-frontal cortex caused shortening of T₂. from 66.9 ± 0.4 to 64.6 ± 0.5 ms. Under these conditions, no change in diffusion MRI was detected. In contrast, the cortex with CBF of 42 ± 7 ml/100 g min showed no change in T₂. Computer simulations accurately predicted these T₂, responses. The present study shows that the acute drop of CBF by 70% causes a negative BOLD that is readily detectable by T₂ MRI at 1.5 T. Thus BOLD may serve as an index of misery perfusion thus revealing viable tissue with increased OER.     

Focal ischemia in cat brain as studied by diffusion-weighted and dynamic susceptibility-contrast magnetic resonance imaging

Diffusion-weighted and susceptibility-contrast-enhanced magnetic resonance imaging were used to monitor the development of focal ischemia in cat brain. Diffusion-sensitized imaging was used to assess early ischemic tissue damage which was confirmed for the latest time point (12 h) with postmortem histological analysis.T*₂-sensitized FLASH was used to measure the first passage of a bolus of FeO particles. Gamma function fitting of R*₂-time curves resulted in 2D maps of relative hemodynamic parameters, including cerebral blood volume and flow. The present data provide indications for cerebral blood flow thresholds for acute as well as for delayed ischemic tissue damage.     

Nonlinear finite-element analysis of the role of dynamic changes inblood perfusion and optical properties in laser coagulation of tissue

A nonlinear finite-element program was developed to simulate the dynamic evolution of coagulation in tissue considering temperature and damage dependence of both the optical properties and blood perfusion rate. These dynamic parameters were derived based on the Arrhenius rate process formulation of thermal damage and kinetics of vasodilation. Using this nonlinear model, we found that the region of increased blood flow that formed at the periphery of the coagulation region significantly reduces the heat penetration. Moreover, increased scattering in the near-surface region prevents light penetration into the deeper region. Therefore, if the dynamic parameters are ignored, a relatively significant overestimation of the temperature rise occurs in a deeper area resulting in an overestimation in predicted depth of coagulation. Mathematical modeling techniques that simulate laser coagulation may not provide reliable information unless they take into account these dynamic parameters     

Absolute cerebral blood flow measured by dynamic susceptibility contrast MRI: a direct comparison with Xe-133 SPECT

Absolute regional cerebral blood flow (CBF) was measured in ten healthy volunteers, using both dynamic susceptibility-contrast (DSC) magnetic resonance imaging (MRI) and Xe-133 SPECT within 4 h. After i.v. injection of Gd-DTPA-BMA (0.3 mmol/kg b.w.), the bolus was monitored with a Simultaneous Dual FLASH pulse sequence (1.5 s/image), providing one slice through brain tissue and a second slice through the carotid artery. Concentration C(t) is proportional to -(1/TE) ln[S(t)/S(0)] was related to CBF as C(t) = CBF [AIF(t) x R(t)], where AIF is the arterial input function and R(t) is the residue function. A singular-value-decomposition-based deconvolution technique was used for retrieval of R(t). Absolute CBF was given by Zierler's area-to-height relation and the central volume principle. For elimination of large vessels (ELV), all MRI-based CBF values exceeding 2.5 times the mean CBF value of the slice were excluded. A correction for partial-volume effects (CPVE) in the artery used for AIF monitoring was based on registration of signal in a phantom with tubes of various diameters (1.5-6.5 mm), providing an individual concentration correction factor applied to AIF data registered in vivo. In the Xe-133 SPECT investigation, 3,000-4,000 MBq of Xe-133 was administered intravenously, and CBF was calculated using the Kanno Lassen algorithm. When ELV and CPVE were applied, DSC-MRI showed average CBF values from the entire slice of 43 +/- 10 ml/(min 100 g) (small-artery AIF) and 48 +/- 17 ml/(min 100 g) (carotid-artery AIF) (mean +/- S.D., n = 10). The corresponding Xe-133-SPECT-based CBF was 33 +/- 6 ml/(min 100 g) (n = 10). The relationships of CBF(MRI) versus CBF(SPECT) showed good linear correlation (r = 0.74-0.83).     

Pathophysiological changes after traumatic brain injury: comparison of two experimental animal models by means of MRI

In an experimental study MRI was used to compare the pathophysiological changes of brain tissue after lateral fluid percussion injury (FPI) versus cold injury (CI) as models of traumatic brain injury (TBI). Two groups of Sprague-Dawley rats (n = 23) were subjected to mild FPI, respectively, CI localized over the right parietal cortex. MRI was performed at different time points including Tlw, T2w and Tlw-CE (Gd-DTPA 0.2 mmol/kg BW) sequences as well as perfusion-weighted imaging with calculation of regional cerebral blood volume (rCBV) and regional cerebral blood flow (rCBF). T2w and Tlw-CE images showed hyperintense areas in the traumatised cortex demonstrating brain edema and blood-brain barrier (BBB)-breakdown increasing up to 12 h. Perfusion-weighted imaging demonstrated a significant decrease of rCBV and rCBF in the ipsilateral cortex of CI animals compared with the contralateral hemisphere. In contrast, rats of the FPI group showed only slight differences in rCBF and rCBV comparing the left and right cortex. The results of our study confirm that both mild FPI and CI produced focal brain edema with concomitant breakdown of the BBB as a model of TBI. Since differences regarding perfusion are much more pronounced in CI our results suggest that, this model more likely seems to reflect pathophysiological changes of brain ischemia, whereas FPI seems to be better suited to model the pathophysiological characteristics of TBI.     

Contrast agents in acute myocardial infarction

The experimental design in examination of acute myocardial infarctions should be valid in terms of flow, perfusion and re-flow after intervention. The contrast agents concentration in experimental studies can be measured by microdialysis. We have assessed the usefulness of different extracellular and blood pool contrast agents for visualization of the area at risk in coronary artery occlusions. The double contrast technique, where Dy-DTPA-BMA was combined with Gd-DTPA-BMA yielded a superior infarct visualization. Blood pool agents for example NC100/150 injection is also promising in first path myocardial perfusion imaging.     

A continuous-flow perfusion system for the maintenance and NMR study of small tissue samples in vitro

To describe and evaluate a novel perfusion system developed to maintain excised tissue in a flowing, oxygenated bathing solution during acquisition of nuclear magnetic resonance (NMR) data, and in addition allow precise data to be acquired continuously while altering the composition of the bathing solution surrounding the tissue. A chamber to house the tissue sample was constructed of interlocking sections of polyethylene tubing, and had approximate internal dimensions of 4 mm in diameter and 4 mm in height. Temperature-controlled, physiologically appropriate buffer solution was pumped via an infusion pump through the chamber, entering and exiting by way of small openings on either end. Immediately surrounding the polyethylene chamber was a tight-fitting four-loop solenoid RF coil. Measured proton NMR parameters were found to be fairly insensitive to the flow rate of the buffer if this coil was used only for reception and a larger-volume transmit-only coil was used for excitation. Temperature control of the sample was successfully implemented between 25 and 40°C. The perfusion system was found to be resistant to the effects of flow rate, as well as a useful tool for the administration of drugs or agents to the tissue. Changes in buffer composition could be performed on the fly without the need to reposition the sample each time a change was made. This avoidance of repositioning was found to yield a fivefold improvement in the precision of T₂ spectral parameters (using frog sciatic nerve as a sample).The authors wish to acknowledge the Canadian Institutes of Health Research (CIHR) for funding and the In Vivo NMR Facility of the University of Alberta for infrastructural support     

Wavelet-based noise reduction for improved deconvolution of time-series data in dynamic susceptibility-contrast MRI

Dynamic susceptibility-contrast (DSC) MRI requires deconvolution to retrieve the tissue residue function R(t) and the cerebral blood flow (CBF). In this study, deconvolution of time-series data was performed by wavelet-transform-based denoising combined with the Fourier transform (FT). Traditional FT-based deconvolution of noisy data requires frequency-domain filtering, often leading to excessive smoothing of the recovered signal. In the present approach, only a low degree of regularisation was employed while the major noise reduction was accomplished by wavelet transformation of data and Wiener-like filtering in the wavelet space. After inverse wavelet transform, the estimate of CBF·R(t) was obtained. DSC-MRI signal-versus-time curves (signal-to-noise ratios 40 and 100) were simulated, corresponding to CBF values in the range 10–60 ml/(min 100 g). Three shapes of the tissue residue function were investigated. The technique was also applied to six volunteers. Simulations showed CBF estimates with acceptable accuracy and precision, as well as independence of any time shift between the arterial input function and the tissue concentration curve. The grey-matter to white-matter CBF ratio in volunteers was 2.4±0.2. The proposed wavelet/FT deconvolution is robust and can be implemented into existing perfusion software. CBF maps from healthy volunteers showed high quality.     

In vivo imaging of cardiac related impedance changes

Electrical impedance tomography (EIT) produces cross-sectional images of the electrical resistivity distribution within the body, made from voltage or current measurements through electrodes attached around the body. The authors describe a gated EIT system to image the cardiogenic electrical resistivity variations and the results of in vivo studies on human subjects. It is shown that the sensitivity of EIT to tissue resistivity variations due to blood perfusion is good enough to image blood flow to the lungs; hence, abnormalities in pulmonary perfusion, such as pulmonary embolism, should appear in EIT images. In addition, more valuable information related to the cardiac activity can be gained from EIT images than from impedance cardiography. It is thus likely that a cardiac output index may be calculable from the average resistivity variations over the ventricles, but considerable research is required before the images can be understood in detail.     

Measured time delay and re-synchronization time in digitalmicrowave radio systems

The transition from analog to digital transmission systems has been slower for electric power utilities than other industrial sectors because of concern that digital transmission system delay times could adversely impact the response time of transfer trip protective relaying equipment. Alcatel Network Systems has completed a comprehensive testing program to measure the absolute time delay and various re-synchronization times through analog and digital transmission systems. The general conclusion is that the worst case absolute time delay of 577 microseconds, VF to VF, through the digital microwave system is approximately one half the delay for a typical analog system. Absolute time delays of 500-600 microseconds should cause no problems to transfer trip protective relaying systems     

Exploring in vivo blood flow dynamics

With the development of improved MR imaging techniques, there has been a resurgence of interest since the early 1980s. Today, MR flow imaging techniques are regarded as important clinical tools for providing detailed in vivo blood flow information. MR phase velocity mapping is a versatile noninvasive flow quantification method that is well suited for analyzing in vivo flow patterns. Since the introduction of quantitative MR velocity imaging methods, clinical and research applications of these techniques have flourished, enabling noninvasive acquisition of detailed quantitative blood flow information. The success of quantitative flow imaging complements recent advances in computational fluid dynamics, which may provide further understanding of cardiovascular mechanics and the genesis and development of cardiovascular disease     

Doppler ultrasound

The use of Doppler today ranges from assessing blood flow in the fetus and umbilical cord, to flow patterns through valves in the heart or monitoring of blood flow to the brain. This article looks at how the Doppler effect is applied in commercial systems, its clinical uses, and research developments. It is concluded that Doppler ultrasound has progressed over the last 30 years from a simple audio signal to a predominantly subjective image format that still requires an operator and/or interpreter skilled in the art. The improvements in velocity estimation methods and gradual changes in the use of Doppler information suggest that this diagnostic modality will continue to evolve. The most likely directions for this evolution appear to be physiological quantification and reduction in dependence on the user through automation of both the system parameters and measurements     

Numerical modelling for simulation and treatment planning of prostate thermal therapy

A 2D transmission line matrix model is used to study thermal transfer in living tissues exposed to laser energy. Damage size because of thermal coagulation in thermal treatment of benign prostate hyperplasia is determined quantitatively. Results show a quasilinear dependency of blood perfusion on temperature at the beginning of coagulation. Immediately thereafter, blood perfusion decreases considerably until it shuts down when the tissue under investigation has been coagulated. Increase in perfusion rate (ω) leads to high values of t₁₀₀, which is the time required to reach a primary zone temperature of about 100 °C, and reflects the increased cooling created by perfusion. The transmission line matrix numerical model predicts the coagulation damage contours; that way, it has a clinical interest in therapy as an aid for clinicians because damage cannot be easily measured within patients. Results are validated through comparison with other researches. Copyright © 2014 John Wiley & Sons, Ltd.     

基于运动学标定和空间插值的机器人定位误差补偿

绝对定位精度是衡量机器人性能的重要指标。为提升工业机器人的绝对定位精度,提出一种融合运动学标定和空间插值的定位误差分级标定的方法。首先基于D-H法建立机器人运动学模型,运用微分运动学理论建立机器人末端位置误差模型,结合IGG3权因子函数采用抗差岭估计辨识了运动学参数。而后基于机器人定位误差空间相似性特点,采用空间插值法对剩余误差进行补偿。最后通过实验对所提出的方法进行了验证。结果表明：机器人定位误差RMS值由补偿前的0.812 mm减小为0.049 mm,精度提高了93.97%。该方法能够有效减小机器人的绝对定位误差,提高定位精度。     

Novel revascularization therapies — TMLR and growth factor-induced angiogenesis monitored with cardiac MRI

4. Summary Employment of cardiac MRI techniques (cine MRI, wall thickening analysis, quantitative MRFPP, MR tissue tagging) allowed non-invasive localization and assessment of early and late changes in myocardial function and perfusion produced by these new approaches of myocardial revascularization. With its precision in assessment of myocardial perfusion and collateral-dependent territories, cardiac MRI techniques may be of excellent use for the evaluation of effects on myocardial function and perfusion as well as longitudinal outcomes in clinical trials with TMLR and angiogenesis therapies in patients with CAD. As growth factor therapies approach phase III clinical trials, such vital questions as the most effective delivery system, dosages and techniques used for treatment-monitoring parameters remain unanswered. In addition, better definitions of patient selection criteria for TMLR and angiogenesis therapies for both short- and long-term maximum benefits are needed at this time. Large-scale clinical trials with cardiac MRI techniques are needed to reliably assess functional and perfusion reserves of the myocardium pre and post TMLR and angiogenesis therapies. MR-based outcome parameters may aid in answering questions pertinent to the new revascularization treatments.     

Dynamic susceptibility contrast perfusion MRI using phase-based venous output functions: comparison with pseudo-continuous arterial spin labelling and assessment of contrast agent concentration in large veins

Objectives

Contrast agent (CA) relaxivities are generally not well established in vivo, and the relationship between frequency/phase shift and magnetic susceptibility might be a useful alternative for CA quantification.

Materials and methods

Twenty volunteers (25–84 years old) were investigated using test–retest pre-bolus dynamic susceptibility-contrast (DSC) magnetic resonance imaging (MRI). The pre-bolus phase-based venous output function (VOF) time integral was used for arterial input function (AIF) rescaling. Resulting cerebral blood flow (CBF) data for grey matter (GM) were compared with pseudo-continuous arterial spin labelling (ASL). During the main bolus CA passage, the apparent spatial shift (pixel shift) of the superior sagittal sinus (seen in single-shot echo-planar imaging (EPI)) was converted to CA concentration and compared with conventional ΔR2*-based data and with a predicted phase-based VOF from the pre-bolus experiment.

Results

The phase-based pre-bolus VOF resulted in a reasonable inter-individual GM CBF variability (coefficient of variation 28 %). Comparison with ASL CBF values implied a tissue R2*-relaxivity of 32 mM^?1 s^?1. Pixel-shift data at low concentrations (data not available at peak concentrations) were in reasonable agreement with the predicted phase-based VOF.

Conclusion

Susceptibility-induced phase shifts and pixel shifts are potentially useful for large-vein CA quantification. Previous predictions of a higher R2*-relaxivity in tissue than in blood were supported.

     

Pre-clinical results with Clariscan™ (NC100150 Injection); experience from different disease models

A superparamagnetic nanoparticle (NC100150 Injection) was investigated in two different animal models; renal perfusion in pigs and tumour imaging in mice. In the pig model, qualitative first-pass perfusion maps following a bolus injection of NC100150 Injection enabled good visualisation of hypoperfused regions of the renal cortex following partial ligation of the renal artery. High temporal resolution was found to be essential to accurately capture the first passage of the contrast agent through the kidney due to the very rapid blood flow in normal renal cortex. In the tumour model (LS174T cells implanted in nude mice), NC100150 Injection was found to cause a gradual (over 60 min) signal increase on Tl-w images in part of the tumours which was attributed to contrast agent leakage from the vascular space to the extravascular space in areas of increased capillary permeability. This observation is consistent with previous reports on the molecular cut-off size for vascular extraction for this tumour cell line. The specific enhancement of tumour tissue suggest potential utility of NC100150 Injection as an angiogenesis marker.