Why perfusion in neonates with congenital heart defects is negative--technical issues related to pulsed arterial spin labeling

Pulsed arterial spin labeling (PASL) perfusion MRI has unique advantages for measuring cerebral blood flow (CBF) in the pediatric population. In neonates with congenital heart defects (CHDs), however, a considerable number of negative CBF values were observed in PASL perfusion images. A set of specific physiological and biophysical conditions were proposed as plausible explanations for this phenomenon, including small body size, low blood flow, prolonged tracer life time (blood T1) and the "shunt" between pulmonary and systemic circulations in CHD. An optimized PASL scheme with a restricted label volume was proposed, and experimental data demonstrated reduced spurious negative values and lower intersubject variability of perfusion measurements in neonates with CHD as compared to standard PASL sequences.     

Cerebral perfusion alterations in epileptic patients during peri-ictal and post-ictal phase: PASL vs DSC-MRI

Non-invasive pulsed arterial spin labeling (PASL) MRI is a method to study brain perfusion that does not require the administration of a contrast agent, which makes it a valuable diagnostic tool as it reduces cost and side effects. The purpose of the present study was to establish the viability of PASL as an alternative to dynamic susceptibility contrast (DSC-MRI) and other perfusion imaging methods in characterizing changes in perfusion patterns caused by seizures in epileptic patients. We evaluated 19 patients with PASL. Of these, the 9 affected by high-frequency seizures were observed during the peri-ictal period (within 5 hours since the last seizure), while the 10 patients affected by low-frequency seizures were observed in the post-ictal period. For comparison, 17/19 patients were also evaluated with DSC-MRI and CBF/CBV. PASL imaging showed focal vascular changes, which allowed the classification of patients in three categories: 8 patients characterized by increased perfusion, 4 patients with normal perfusion and 7 patients with decreased perfusion. PASL perfusion imaging findings were comparable to those obtained by DSC-MRI. Since PASL is a) sensitive to vascular alterations induced by epileptic seizures, b) comparable to DSC-MRI for detecting perfusion asymmetries, c) potentially capable of detecting time-related perfusion changes, it can be recommended for repeated evaluations, to identify the epileptic focus, and in follow-up and/or therapy-response assessment.     

Abnormalities of cerebral blood flow in multiple sclerosis: A pseudocontinuous arterial spin labeling MRI study

Arterial spin labeling (ASL) is a noninvasive technique that can measure cerebral blood flow (CBF). To our knowledge, there is no study that examined regional CBF of multiple sclerosis (MS) patients by using this technique. The present study assessed the relationship between clinical presentations and functional imaging data in MS using pseudocontinuous arterial spin labeling (pCASL). Twenty-seven patients with MS and 24 healthy volunteers underwent magnetic resonance imaging and pCASL to assess CBF. Differences in CBF between the two groups and the relationships of CBF values with the T2-hyperintense volume were evaluated. Compared to the healthy volunteers, reduced CBF was found in the bilateral thalami and right frontal region of the MS patients. The volume of the T2-hyperintense lesion was negatively correlated with regional CBF in some areas, such as both thalami. Our results suggest that demyelinated lesions in MS mainly have a remote effect on the thalamus and that the measurement of CBF using ASL could be an objective marker for monitoring disease activity in MS.     

Absolute quantification of cerebral blood flow: correlation between dynamic susceptibility contrast MRI and model-free arterial spin labeling

Purpose

To compare absolute cerebral blood flow (CBF) estimates obtained by model-free arterial spin labeling (ASL) and dynamic susceptibility contrast MRI (DSC-MRI), corrected for partial volume effects (PVEs).

Methods

CBF was measured using DSC-MRI and model-free ASL (quantitative signal targeting with alternating radiofrequency labeling of arterial regions) at 3 T in 15 subjects with brain tumor, and the two modalities were compared with regard to CBF estimates in normal gray matter (GM) and DSC-to-ASL CBF ratios in selected tumor regions. The DSC-MRI CBF maps were calculated using a global arterial input function (AIF) from the sylvian-fissure region, but, in order to minimize PVEs, the AIF time integral was rescaled by a venous output function time integral obtained from the sagittal sinus.

Results

In GM, the average DSC-MRI CBF estimate was 150±45 ml/(min 100 g) (mean±SD) while the corresponding ASL CBF was 44±10 ml/(min 100 g). The linear correlation between GM CBF estimates obtained by DSC-MRI and ASL was r=.89, and observed DSC-to-ASL CBF ratios differed by less than 3% between GM and tumor regions.

Conclusions

A satisfactory positive linear correlation between the CBF estimates obtained by model-free ASL and DSC-MRI was observed, and DSC-to-ASL CBF ratios showed no obvious tissue dependence.     

准连续性动脉自旋标记技术在磁共振系统上的序列实现和参数优化

准连续性动脉自旋标记技术(pCASL)是一种新兴的动脉自旋标记脑灌注成像技术(ASL)：一方面,它克服了连续性动脉自旋标记技术(CASL)需要独立发射线圈的硬件限制;另一方面,也避免了脉冲式动脉自旋标记技术(PASL)带来的标记效率低的影响．为了在 1.5 T 磁共振系统上开发一款可稳定应用于临床扫描的 pCASL 序列;并使用该序列准确获得反
应灌注功能的局部脑血流量值(Regional Cerebral Blood Flow, rCBF)．该文利用水模测试pCASL 序列,验证了标记部分的标记性能并通过人体实验,优化了协议中标记位置中心到成像层面中心的距离和标记部分结束点到成像脉冲开始前的等待时间这两项参数．基于优化了参数的 pCASL 协议,扫描 12 组正常志愿者,观测灌注信号分布情况,并对特定灰质区域定量计算,对比不同个体该区域的 rCBF 值．通过人体实验,经验性地确定了延迟时间为 1 200 ms、标记距离为 70 mm 时灌注图像的信噪比达到最优．将两项优化后的参数存入协议中,并使用协议扫描,共获取 12 组结果,其中的 10 组都表明灌注信号稳定均匀,并且灰质区域的 CBF 值同经验结果一致．该工作在1.5 T 的磁共振系统上成功实现了 pCASL序列,经优化参数后的协议扫描,可以获得准确稳定的脑部灌注信号．
     

Atlas-based and DTI-guided quantification of human brain cerebral blood flow: Feasibility,quality assurance,spatial heterogeneity and age effects

Accurate and noninvasive quantification of regional cerebral blood perfusion (CBF) of the human brain tissue would advance the study of the complex interplay between human brain structure and function, in both health and disease. Despite the plethora of works on CBF in gray matter, a detailed quantitative white matter perfusion atlas has not been presented on healthy adults using the International Consortium for Brain Mapping atlases. In this study, we present a host of assurance measures such as temporal stability, spatial heterogeneity and age effects of regional and global CBF in selected deep, cortical gray matter and white matter tracts identified and quantified using diffusion tensor imaging (DTI). We utilized whole brain high-resolution DTI combined with arterial spin labeling to quantify regional CBF on 15 healthy adults aged 23.2–57.1 years. We present total brain and regional CBF, corresponding volume, mean diffusivity and fractional anisotropy spatial heterogeneity, and dependence on age as additional quality assurance measures to compare with published trends using both MRI and nuclear medicine methods. Total CBF showed a steady decrease with age in gray matter (r=?0.58; P= .03), whereas total CBF of white matter did not significantly change with age (r= 0.11; P= .7). This quantitative report offers a preliminary baseline of CBF, volume and DTI measurements for the design of future multicenter and clinical studies utilizing noninvasive perfusion and DT-MRI.     

On the sensitivity of ASL MRI in detecting regional differences in cerebral blood flow

Arterial-spin-labeling (ASL) magnetic resonance imaging (MRI) provides a noninvasive tool to measure cerebral blood flow (CBF) and is increasingly used as a surrogate for baseline neural activity. However, the power of ASL MRI in detecting CBF differences between patient and control subjects is hampered by inter-subject variations in global CBF, which are associated with non-neural factors and may contribute to the noise in the across-group comparison. Here, we investigated the sensitivity of this technique and proposed a normalization strategy to better detect such a difference. A “model” situation was employed in which two visual stimuli (i.e. cross fixation and flashing checkerboard) were presented to two groups of subjects to mimic “control” and “patient” groups (N=7 for each group), respectively. It was found that absolute CBF (aCBF) in the occipital lobe in the checkerboard group was 26.0% greater compared to the fixation group, but the level of significance was modest (P=.03). In contrast, when normalizing the CBF with whole-brain CBF or CBF in a reference region [termed relative CBF (rCBF)], the statistical significance was improved considerably (P<.003). For voxel-based analysis, the rCBF indices correctly detected CBF differences in the occipital lobe in the across-group comparison, while aCBF failed to detect any significant cluster using the same statistical threshold. We also performed Monte Carlo simulation to confirm the experimental findings and found that the power improvement was most pronounced when signal-to-noise-ratio is moderate and the underlying CBF difference was small. The simulation also showed that, with the proposed normalization, a detection power of 80% can be achieved using a sample size of about 20. In summary, rCBF is a more sensitive index to detect small differences in CBF, rather than the much-sought-after aCBF, since it reduces data noise caused by inter-subject variations in global CBF.     

Assessment of clinical data of nonlinear stochastic deconvolution versus block-circulant singular value decomposition for quantitative dynamic susceptibility contrast magnetic resonance imaging

Dynamic susceptibility contrast magnetic resonance imaging (DSC-MRI) allows the noninvasive assessment of brain hemodynamics alterations by quantifying, via deconvolution, the cerebral blood flow (CBF) and mean transit time (MTT). Singular value decomposition (SVD) and block-circulant SVD (cSVD) are the most widely adopted deconvolution method, although they bear some limitations, including unphysiological oscillations in the residue function and bias in the presence of delay and dispersion between the tissue and the arterial input function. A nonlinear stochastic regularization (NSR) has been proposed, which performs better than SVD and cSVD on simulated data both in the presence and absence of dispersion. Moreover, NSR allows to quantify the dispersion level. Here, cSVD and NSR are compared for the first time on a group of nine patients with severe atherosclerotic unilateral stenosis of internal carotid artery before and after carotid stenting to investigate the effect of arterial dispersion. According to region of interest-based analysis, NSR characterizes the pathologic tissue more accurately than cSVD, thus improving the quality of the information provided to physicians for diagnosis. In fact, in 7 (78%) of the 9 subjects, CBF and MTT maps provided by NSR allow to correctly identify the pathologic hemisphere to the physician. Moreover, by emphasizing the difference between pathologic and healthy tissues, NSR may be successfully used to monitor the subject's recovery after the treatment and/or surgery. NSR also generates dispersion level and non-dispersed CBF and MTT maps. The dispersion level provides information on CBF and MTT estimates reliability and may also be used as a clinical indicator of pathological tissue state complementary to CBF and MTT, thus increasing the clinical information provided by DSC-MRI analysis.     

An alternative viewpoint of the similarities and differences of SVD and FT deconvolution algorithms used for quantitative MR perfusion studies

Quantitative cerebral blood flow (CBF) values can be determined from residue function estimates obtained from magnetic resonance dynamic susceptibility contrast (DSC) perfusion studies using a variety of deconvolution approaches. However, there are significant differences between the CBF estimates obtained, differences that are not simply due to minor details of the implementation of the algorithms. The standard singular value decomposition (sSVD) shows a variation of CBF values with arterial-tissue delay (ATD) not present with the Fourier transform deconvolution algorithm. Fourier transform deconvolution and the newly suggested delay-invariant SVD algorithm implementations provide CBF estimates whose accuracy changes with tissue mean transit times (MTTs). Techniques combining sSVD with deliberate ATD manipulation have been proposed to compensate for this inaccuracy. Other studies indicate that CBF changes related to slice position in a multislice study, and other experimental factors, can be reduced using interpolative deconvolution algorithms. In this review, we use both time-domain and frequency-domain analysis to show the underlying theoretical relationships between these many approaches to obtain "the best" CBF estimate. This model allows us to better understand the similarities and differences, advantages and disadvantages between these variants of the deconvolution algorithms used in DSC perfusion studies.     

Comparison of multislice and single-slice acquisitions for pulsed arterial spin labeling measurements of cerebral perfusion

Multislice Q2TIPS is a widely used pulsed arterial spin labeling (PASL) technique for efficient and accurate quantification of cerebral blood flow (CBF). Slices are typically acquired inferior to superior from a tagging plane. Superior slices show signal loss greater than the loss expected from blood T1 decay. In order to assess the reasons for this additional signal loss, three single-slice acquisition studies were compared to multislice acquisition (six slices) in healthy volunteers. In Study 1 (n=8), the tagging plane was fixed in location, and the inversion time (TI2) was 1500 ms for each slice. For Study 2 (n=12), the tagging plane was fixed as in Study 1; however, TI2 increased as slices were acquired further from the tagging plane. In Study 3 (n=9), the tagging plane was kept adjacent to the imaging slice, and TI2 was 1500 ms for every slice. Gray matter (GM) and white matter (WM) signal-to-noise ratio (SNR) and CBF were measured per slice. GM SNR from single-slice acquisitions was significantly higher at slices 4-6 in Study 2 and at slices 2-6 in Study 3 compared to multislice acquisitions. Signal loss in distal slices of multislice acquisitions can be attributed to the destruction of tagged bolus in addition to blood T1 decay. If limited brain coverage is acceptable, perfusion images with greater SNR are achievable with limited slices and placement of the tagging region immediately adjacent to the site of interest.     

Quantitative assessment of dynamic PET imaging data in cancer imaging

Clinical imaging in positron emission tomography (PET) is often performed using single-time-point estimates of tracer uptake or static imaging that provides a spatial map of regional tracer concentration. However, dynamic tracer imaging can provide considerably more information about in vivo biology by delineating both the temporal and spatial pattern of tracer uptake. In addition, several potential sources of error that occur in static imaging can be mitigated. This review focuses on the application of dynamic PET imaging to measuring regional cancer biologic features and especially in using dynamic PET imaging for quantitative therapeutic response monitoring for cancer clinical trials. Dynamic PET imaging output parameters, particularly transport (flow) and overall metabolic rate, have provided imaging end points for clinical trials at single-center institutions for years. However, dynamic imaging poses many challenges for multicenter clinical trial implementations from cross-center calibration to the inadequacy of a common informatics infrastructure. Underlying principles and methodology of PET dynamic imaging are first reviewed, followed by an examination of current approaches to dynamic PET image analysis with a specific case example of dynamic fluorothymidine imaging to illustrate the approach.     

Effect of high dose isoflurane on cerebral blood flow in macaque monkeys

The effect of high dose isoflurane on cerebral blood flow (CBF) was investigated in adult macaque monkeys receiving 1% to 2% isoflurane with the pseudo continuous arterial-spin-labeling (pCASL) MRI technique. High concentration (2%) of isoflurane resulted in significant increase in the mean CBF of the global, cortical, subcortical regions and the regional CBF in all subcortical structures and most cortical structures (such as motor cortex, anterior cingulate cortex, but not media prefrontal cortex). In addition, the changes of regional CBF in the affected regions correlated linearly with increasing isoflurane concentrations. The study demonstrates region-specific CBF abnormal increase in adult macaque monkeys under high dose (2%) isoflurane and suggests that the brain functionality in the corresponding structures may be affected and need to be taken consideration in either human or non-human primate neuroimaging studies.     

Deconvolution with simple extrapolation for improved cerebral blood flow measurement in dynamic susceptibility contrast magnetic resonance imaging during acute ischemic stroke

Magnetic resonance (MR) perfusion imaging is a clinical technique for measuring brain blood flow parameters during stroke and other ischemic events. Ischemia in brain tissue can be difficult to accurately measure or visualize when using MR-derived cerebral blood flow (CBF) maps. The deconvolution techniques used to estimate flow can introduce a mean transit time-dependent bias following application of noise stabilization techniques. The underestimation of the CBF values, greatest in normal tissues, causes a decrease in the image contrast observed in CBF maps between normally perfused and ischemic tissues; resulting in ischemic areas becoming less conspicuous. Through application of the proposed simple extrapolation technique, CBF biases are reduced when missing high-frequency signal components in the MR data removed during deconvolution noise stabilization are restored. The extrapolation approach was compared with other methods and showed a statistically significant increase in image contrast in CBF maps between normal and ischemic tissues for white matter (P<.05) and performed better than most other methods for gray matter. Receiver operator characteristic curve analysis demonstrated that extrapolated CBF maps better-detected penumbral regions. Extrapolated CBF maps provided more accurate CBF estimates in simulations, suggesting that the approach may provide a better prediction of outcome in the absence of treatment.     

Comments on the design of chemical libraries for screening

Different representations of molecules, based ondistinct sets of properties can yield differentperspectives of the issues involved in library design.In particular, different chemical representations cangive rise to very different estimates of requiredlibrary sizes. We provide a preliminary mathematicalframework that examines the size of libraries requiredto adequately sample the spaces corresponding to somecommonly used property sets. Introduction ofconformational flexibility is also discussed as ameans of increasing coverage of chemical libraries,while at the same time considering the thermodynamicconsequences of flexibility upon detectable activity.Our theoretical analysis reveals that the propertyspaces currently in use are extremely large andunlikely to provide adequate discrimination amongcompounds.     

Effects of variable blast pressures on blood flow and oxygen saturation in rat brain as evidenced using MRI

It has been recognized that primary blast waves may result in neurotrauma in soldiers in theater. A new type of contrast used in magnetic resonance imaging (MRI), susceptibility-weighted imaging (SWI), has been developed that is based on the different susceptibility levels in diverse tissues and can detect decreases in cerebral blood flow (CBF) using inferred oxygen saturation changes in tissue. In addition, a continuous arterial spin-labeled (ASL) MRI sequence was used as a direct measure of regional CBF within the brain tissue. Animals were subjected to whole-body blast exposures of various overpressures within a gas-driven shock tube. When exposed to low levels of overpressure, most rats demonstrated no obvious changes between pre- and postexposure in the conventional MR images. CBF changes measured by SWI and ASL were significantly higher for the overpressure exposed groups as compared to the sham group and tended to increase with pressure increases at the highest two pressures. In the hippocampus, all blast animals had a reduction in the CBF consistently in the range of 0-27%. In summary, low levels of primary blast pressure exposure demonstrated a significant physiologic effect to the brain up to 72 h postexposure.     

Effects of blood ΔR2* non-linearity on absolute perfusion quantification using DSC-MRI: Comparison with Xe-133 SPECT

Purpose

To evaluate whether a non-linear blood ΔR₂*-versus-concentration relationship improves quantitative cerebral blood flow (CBF) estimates obtained by dynamic susceptibility contrast (DSC) MRI in a comparison with Xe-133 SPECT CBF in healthy volunteers.

Material and Methods

Linear as well as non-linear relationships between ΔR₂* and contrast agent concentration in blood were applied to the arterial input function (AIF) and the venous output function (VOF) from DSC-MRI. To reduce partial volume effects in the AIF, the arterial time integral was rescaled using a corrected VOF scheme.

Results

Under the assumption of proportionality between the two modalities, the relationship CBF(MRI) = 0.58CBF(SPECT) (r = 0.64) was observed using the linear relationship and CBF(MRI) = 0.51CBF(SPECT) (r = 0.71) using the non-linear relationship.

Discussion

A smaller ratio of the VOF time integral to the AIF time integral and a somewhat better correlation between global DSC-MRI and Xe-133 SPECT CBF estimates were observed using the non-linear relationship. The results did not, however, confirm the superiority of one model over the other, potentially because realistic AIF signal data may well originate from a combination of blood and surrounding tissue.     

Probing the excitation spectrum of a fermi gas in the BCS-BEC crossover regime

We measure excitation spectra of an ultracold gas of fermionic (40)K atoms in the BCS-Bose-Einstein-condensation (BEC) crossover regime. The measurements are performed with a novel spectroscopy that employs a small modulation of the B field close to a Feshbach resonance to give rise to a modulation of the interaction strength. With this method we observe both a collective excitation as well as the dissociation of fermionic atom pairs in the strongly interacting regime. The excitation spectra reveal the binding energy or excitation gap for pairs in the crossover region.     

Relationship between the hemodynamic changes on multi-Td pulsed arterial spin labeling images and the degrees of cerebral artery stenosis

Objective

To explore the relationship between the hemodynamic changes on multi-Td (delay time) pulsed arterial spin labeling (PASL) images and the degrees of cerebral artery stenosis, and to evaluate the value of multi-Td PASL in detecting the signal changes in cerebral arteries with stenosis.

Patients and methods

29 patients with less than 50% stenosis (mild stenosis group) and 22 patients with 50%–69% stenosis (moderate stenosis group) in M1 segment of unilateral middle cerebral artery (MCA) were included in this study. The degrees of MCA stenosis were measured using time of flight MR angiography (TOF MRA). Multi-Td PASL imaging was performed to detect the signal changes in bilateral MCA. We selected and hand-drew bilateral symmetric branches of MCA as regions of interest (ROIs) on eight-Td PASL images. The intensities of ROIs were measured, and the time-signal intensity curves were acquired by post-processing on a MR workstation. SPSS19.0 statistical software was used for statistics. The differences in the peak intensities and the times to peak intensities between the normal and narrowed sides of the mild and moderate stenosis groups were respectively examined by paired-samples t test. The differences in the changes of peak intensities and times to peak intensity of the two sides between the mild and moderate stenosis groups were examined by independent samples t test. A p value less than 0.05 was considered statistically significant.

Result

There were significant difference in the peak intensities (t = − 2.720, p = 0.011 < 0.05) and no significant difference in the times to peak intensities (t = − 1.279, p = 0.212 > 0.05) between the normal and narrowed sides of the mild stenosis group. There were both significant differences in the peak intensities (t = − 6.076, p = 0.000 < 0.05) and times to peak intensities (t = 7.232, p = 0.000 < 0.05) between the normal side and narrowed side of the moderate stenosis group. There were both significant differences in the changes of peak intensities (t = − 2.11, p = 0.040 < 0.05) and times to peak intensity (t = − 4.23, p = 0.000 < 0.05) between the mild and moderate stenosis groups.

Conclusion

The hemodynamic changes on multi-Td PASL images were different with the degrees of cerebral artery stenosis. Moderate stenosis means greater hemodynamic changes in the arteries than mild stenosis. Multi-Td PASL imaging is a promising means to evaluate the hemodynamic changes in cerebral arteries with stenosis.     

MRI measurement of blood-brain barrier permeability following spontaneous reperfusion in the starch microsphere model of ischemia

Quantification of the acute increases in blood-brain barrier (BBB) permeability that occur subsequent to experimental ischemic injury has been limited to single time-point, invasive methodologies. Although permeability can be qualitatively assessed to visualise regional changes during sequential studies on the same animal using contrast-enhanced magnetic resonance imaging (MRI), quantitative information on the magnitude of change is required to compare barrier function during sequential studies on the same animal or between different animals. Recently, improvements in MRI tracer kinetic models and in MR hardware design mean that an estimate of permeability in vivo can now be obtained with acceptable accuracy and precision. We report here the use of such methods to study acute changes following spontaneous reperfusion in an animal model of ischemia. We have obtained estimates of BBB permeability following spontaneous reperfusion, subsequent to forebrain ischemia by unilateral carotid injection of starch microspheres in the rat. T2*-weighted and diffusion-trace imaging were used to monitor the initial reduction in CBF and the time-course of ischemia, respectively. Following reperfusion, an intraveneous bolus of dimeglumine gadopentetate (Gd-DTPA) and horseradish peroxidase (HRP) was given during a continuous acquisition of T1 maps with a 48 s temporal resolution. Permeability maps were constructed using a 4-compartment model; K(trans), the permeability-surface area product of the capillary walls was estimated to be 9.2 +/- 0.6 x 10(-4) min(-1) in the cortex. Visualisation of the regional extent of HRP extravasation on histological sections following termination of the experiment demonstrated very little correspondence to the region of Gd-DTPA leakage. Quantitative MRI assessment of BBB permeability following ischemia-reperfusion is consistent with published values obtained by invasive methods. Differences between Gd-DTPA-enhancement and HRP may reflect differences in the molecular size of the tracers.