Estimates Of Cerebral Blood Volume Research Articles

Comparison between intensity normalization techniques for dynamic susceptibility contrast (DSC)‐MRI estimates of cerebral blood volume (CBV) in human gliomas

To compare "standardization," "Gaussian normalization," and "Z-score normalization" intensity transformation techniques in dynamic susceptibility contrast magnetic resonance imaging (DSC-MRI) estimates of cerebral blood volume (CBV) in human gliomas. DSC-MRI is a well-established biomarker for CBV in brain tumors; however, DSC-MRI estimates of CBV are semiquantitative. The use of image intensity transformation algorithms provides a mechanism for obtaining quantitatively similar CBV maps with the same intensity scaling. The coefficient of variance (CV) in normal-appearing white matter and relative contrast between tumor regions and normal tissue was compared between the three CBV transformations across five different MR scanners in 96 patients with gliomas. The results suggest all normalization techniques improved variability and relative tumor contrast of CBV measurements compared with nonnormalized CBV maps. The results suggest Gaussian normalization of CBV maps provided slightly lower CV in normal white matter and provided slightly higher tumor contrast for glioblastomas (WHO grade IV) compared with other techniques. The results suggest Gaussian normalization of leakage-corrected CBV maps may be the best choice for image intensity correction for use in large-scale, multicenter clinical trials where MR scanners and protocols vary widely due to ease of implementation, lowest variability, and highest tumor to normal tissue contrast.

Measuring brain oxygenation in humans using a multiparametric quantitative blood oxygenation level dependent MRI approach

Quantitative blood oxygenation level dependent approaches have been designed to obtain quantitative oxygenation information using MRI. A mathematical model is usually fitted to the time signal decay of a gradient-echo and spin-echo measurements to derive hemodynamic parameters such as the blood oxygen saturation or the cerebral blood volume. Although the results in rats and human brain have been encouraging, recent studies have pointed out the need for independent estimation of one or more variables to increase the accuracy of the method. In this study, a multiparametric quantitative blood oxygenation level dependent approach is proposed. A combination of arterial spin labeling and dynamic susceptibility contrast methods were used to obtain quantitative estimates of cerebral blood volume and cerebral blood flow. These results were combined with T 2 and T(2) measurements to derive maps of blood oxygen saturation or cerebral metabolic rate of oxygen. In 12 normal subjects, a mean cerebral blood volume of 4.33 ± 0.7%, cerebral blood flow of 43.8 ± 5.7 mL/min/100 g, blood oxygen saturation of 60 ± 6% and cerebral metabolic rate of oxygen 157 ± 23 μmol/100 g/min were found, which are in agreement with literature values. The results obtained in this study suggest that this methodology could be applied to study brain hypoxia in the setting of pathology.

Perfusion parameters derived from bolus-tracking perfusion imaging are immune to tracer recirculation

To investigate the impact of tracer recirculation on estimates of cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT). The theoretical model used to derive CBF, CBV, and MTT was examined. CBF and CBV estimates with and without tracer recirculation were compared in computer simulations to examine the effects of tracer recirculation. The equations used to derive CBF, CBV, and MTT assume that the arterial input function and tissue tracer signals define the input and output signals, respectively, of a linear time-invariant system. As a result of the principle of superposition, these perfusion parameters are immune to tracer recirculation, which was confirmed by computer simulation. However, limited acquisition durations can lead to CBV and CBF errors of up to 50%. Tracer recirculation does not impact estimation of CBF, CBV, or MTT. However, previous approaches used to remove recirculation effects may be beneficial when used to compensate for limited acquisition durations in which the passage of the bolus is not adequately captured.

Comparison of quantitative dynamic susceptibility-contrast MRI perfusion estimates obtained using different contrast-agent administration schemes at 3 T

Absolute cerebral perfusion parameters were obtained by dynamic susceptibility contrast magnetic resonance imaging (DSC-MRI) carried out using different contrast-agent administration protocols. Sixteen healthy volunteers underwent three separate DSC-MRI examinations each, receiving single-dose (0.1 mmol/kg b.w.) gadobutrol, double-dose gadobutrol and single-dose gadobenate-dimeglumine on different occasions. DSC-MRI was performed using single-shot gradient-echo echo-planar imaging at 3 T. The arterial input functions (AIFs) were averages (4–9 pixels) of arterial curves from middle cerebral artery branches, automatically identified according to standard criteria. Absolute estimates of cerebral blood volume (CBV), cerebral blood flow (CBF) and mean transit time (MTT) were calculated without corrections for non-linear contrast-agent (CA) response in blood or for different T2* relaxivities in tissue and artery. Perfusion estimates obtained using single and double dose of gadobutrol correlated moderately well, while the relationship between estimates obtained using gadobutrol and gadobenate-dimeglumine showed generally lower correlation. The observed degree of CBV and CBF overestimation, compared with literature values, was most likely caused by different T2* relaxivities in blood and tissue in combination with partial-volume effects. The present results showed increased absolute values of CBV and CBF at higher dose, not predicted by the assumption of a quadratic response to contrast-agent concentration in blood. This indicates that the signal components of measured AIFs were not purely of arterial origin and that arterial signal components were more effectively extinguished at higher CA dose. This study also indicates that it may not be completely straightforward to compare absolute perfusion estimates obtained with different CA administration routines.

On the measurement of absolute cerebral blood volume (CBV) using vascular‐space‐occupancy (VASO) MRI

Recently, a vascular-space-occupancy (VASO) MRI technique was developed for quantitative assessment of cerebral blood volume (CBV). This method uses the T(1)-shortening effect of gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA) with imaging parameters chosen that null the precontrast blood magnetization but allow the postcontrast blood magnetization to recover to equilibrium. A key advantage of VASO CBV estimation is that it provides a straightforward procedure for converting MR signals to absolute physiologic values. However, as with other T(1)-based steady-state approaches, several important factors need to be considered that influence the accuracy of CBV values obtained with VASO MRI. Here, the transverse relaxation (T(2)/T(2) (*)) effect in VASO MRI was investigated using multiecho spin-echo and gradient-echo experiments, resulting in underestimation of CBV by 14.9% +/- 1.1% and 16.0% +/- 2.5% for spin echo (TE = 10 ms) and gradient echo (TE = 6 ms), respectively. In addition, the influence of contrast agent clearance was studied by acquiring multiple postcontrast VASO images at 2.2-min intervals, which showed that the concentration of Gd-DTPA in the first 14 min (single dose) was sufficient for the blood magnetization to fully recover to equilibrium. Finally, the effect of vascular Gd-DTPA leakage was assessed for scalp tissue, and signal extrapolation as a function of postinjection time was demonstrated to be useful in minimizing the associated errors. Specific recommendations for VASO MRI acquisition and processing strategies are provided.

Attempts to improve absolute quantification of cerebral blood flow in dynamic susceptibility contrast magnetic resonance imaging: a simplified T1-weighted steady-state cerebral blood volume approach

Attempts to retrieve absolute values of cerebral blood flow (CBF) by dynamic susceptibility contrast magnetic resonance imaging (DSC-MRI) have typically resulted in overestimations. To improve DSC-MRI CBF estimates by calibrating the DSC-MRI-based cerebral blood volume (CBV) with a corresponding T1-weighted (T1W) steady-state (ss) CBV estimate. 17 volunteers were investigated by DSC-MRI and 133Xe SPECT. Steady-state CBV calculation, assuming no water exchange, was accomplished using signal values from blood and tissue, before and after contrast agent, obtained by T1W spin-echo imaging. Using steady-state and DSC-MRI CBV estimates, a calibration factor K = CBV(ss)/CBV(DSC) was obtained for each individual. Average whole-brain CBF(DSC) was calculated, and the corrected MRI-based CBF estimate was given by CBF(ss) = K x CBF(DSC). Average whole-brain SPECT CBF was 40.1+/-6.9 ml/min x 100 g, while the corresponding uncorrected DSC-MRI-based value was 69.2+/-13.8 ml/min x 100 g. After correction with the calibration factor, a CBF(ss) of 42.7+/-14.0 ml/min x 100 g was obtained. The linear fit to CBF(ss)-versus-CBF(SPECT) data was close to proportionality (R = 0.52). Calibration by steady-state CBV reduced the population average CBF to a reasonable level, and a modest linear correlation with the reference 133Xe SPECT technique was observed. Possible explanations for the limited accuracy are, for example, large-vessel partial-volume effects, low post-contrast signal enhancement in T1W images, and water-exchange effects.

Estimate of vascular permeability and cerebral blood volume using Gd‐DTPA contrast enhancement and dynamic T2*‐weighted MRI

To develop a numerical approach for estimation of vascular permeability from dynamic T2*-weighted imaging, a technique routinely used to measure cerebral blood volume (CBV) and flow in gliomas. This study describes a process for estimating both the gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA) transvascular transfer constant and CBV from dynamic T2*-weighted images. The algorithm was applied to data from the brains of 12 patients with grade IV gliomas. The stability of the method was assessed. Estimates of CBV by this technique were compared to those of the conventional method. The algorithm was found to be insensitive to noise and to generate stable voxel-by-voxel estimates of permeability and CBV. Using a single imaging acquisition, the three most important vascular properties, CBV, cerebral blood flow (CBF), and permeability, can be estimated. This approach may have potential in clinical evaluation of patients with brain tumor or acute ischemic stroke.

Experimental Estimates of the Constants Relating Signal Change to Contrast Concentration for Cerebral Blood Volume by T2* MRI

Estimates of cerebral blood volume (CBV) obtained from dynamic contrast T2(*)-weighted magnetic resonance imaging (MRI) tend to be significantly higher than values obtained by other methods. This may relate to the common assumption that the proportionality constants relating signal change to contrast concentration are equal in tissue and artery. To test this hypothesis and provide estimates for the ratio of those proportionality constants, the authors compared measurements of CBV by both MRI and computed tomography (CT) scans in nine healthy volunteers obtained using identical kinetic paradigms for the two imaging modalities. Both boluses and infusions of contrast were studied. Measurements were made in nine anatomic regions of interest of the cerebral hemispheres bilaterally. Cerebral blood volume values obtained by CT were generally lower than those obtained by MRI, especially in the cerebral cortex. As a result, the calculated values of the ratios of proportionality constants relating signal change to concentration in tissue and artery after bolus injections were significantly less than 1 in cortex (0.69) and white matter (0.76), although not in deep gray matter structures (0.87). Values of the ratios based on infusion measurements were closer to 1. In addition, CBV measurement errors with bolus MRI were significantly larger than those observed with infusion MRI or by CT. The reasons that the constants differ from 1 and for the larger variance of bolus MRI are discussed in terms of the T2* signal mechanisms. These studies help define the magnitude by which CBV is overestimated with typical T2*-weighted perfusion imaging. Infusion measurements of CBV can reduce the variance intrinsic to T2* MRI and lessen the likelihood of type II error.

Intracranial mass lesions: dynamic contrast-enhanced susceptibility-weighted echo-planar perfusion MR imaging.

Dynamic contrast agent-enhanced perfusion magnetic resonance (MR) imaging provides physiologic information that complements the anatomic information available with conventional MR imaging. Analysis of dynamic data from perfusion MR imaging, based on tracer kinetic theory, yields quantitative estimates of cerebral blood volume that reflect the underlying microvasculature and angiogenesis. Perfusion MR imaging is a fast and robust imaging technique that is increasingly used as a research tool to help evaluate and understand intracranial disease processes and as a clinical tool to help diagnose, manage, and understand intracranial mass lesions. With the increasing number of applications of perfusion MR imaging, it is important to understand the principles underlying the technique. In this review, the essential underlying physics and methods of dynamic contrast-enhanced susceptibility-weighted echo-planar perfusion MR imaging are described. The clinical applications of cerebral blood volume maps obtained with perfusion MR imaging in the differential diagnosis of intracranial mass lesions, as well as the pitfalls and limitations of the technique, are discussed. Emphasis is on the clinical role of perfusion MR imaging in providing insight into the underlying pathophysiology of cerebral microcirculation.

Neonatal Intensive Care Applications of Near-Infrared Spectroscopy

Near-infrared spectroscopy (NIRS) is a noninvasive technique for assessing cerebral hemodynamic variables and oxidative status in the neonatal intensive care setting. It can be performed for extended periods of time at the bedside without interfering with routine patient care. NIRS appears to have the ability to not only assess relative changes in oxygenated and deoxygenated hemoglobin, total hemoglobin, and cytochrome aa3, but it can also produce estimates of cerebral blood volume and cerebral blood flow. Research data document significant changes in these hemodynamic variables with patient activity and clinical interventions in both premature and term infants. NIRS may evolve into an important diagnostic and prognostic tool for neonatal neurologic outcome.

Estimation of cerebral blood volume and transit time in neonates from quick oxygen increases measured by near-infrared spectrophotometry.

Quick oxygen increases are used to estimate the cerebral blood flow (cbf) or cerebral haemoglobin flow (cHbf) in neonates by near infrared spectrophotometry (NIRS) (Edwards et al, Skov et al., Bucher et al.). One of the essential assumptions for the correct estimation of cbf by the Fick principle is, that the time a bolus of tracer needs to pass the cerebral compartment - the so-called transit time (tt) - exceeds 6s to 8s. This paper describes a way of estimating the tt.KeywordsCerebral Blood FlowPulse OximeterCerebral Blood VolumeOxygen IndexIntegration PeriodThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Estimation of cerebral oxygen utilization rate by single-bolus 15O2 inhalation and dynamic positron emission tomography.

This study shows that regional CMRO2 can be estimated by means of nonlinear regression using dynamic positron emission tomographic data acquired during 1 min following single-bolus inhalation of 15O2. The feasibility of simultaneous estimation of CBF, cerebral blood volume (CBV), oxygen extraction ratio (OER), and CMRO2 was assessed by simulations using the model of Mintun et al. Four oxygen metabolic measurements, each consisting of a CBF, CBV, and 15O2 bolus study, were carried out on three volunteers. Regional values for CBF, CBV, OER, and CMRO2 were derived in two ways: from the fits of the time-activity curves of the dynamic 15O2 bolus study alone [CMRO2(fit)] and from the three separate studies [CMRO2 (control)]. For the 56 regions of interest analyzed, using a fit interval of 60 s, CMRO2(fit) was 93.4 +/- 7.8% of CMRO2(control) (mean +/- SD) with a correlation coefficient of r = 0.95. CMRO2(control) ranged from 87 to 290 mumol/min/100 g. Individual simultaneous estimates of CBF, CBV, and OER were not reliable. Finally, we found that the validity of the model was limited in practice to the first minute after tracer inhalation.

Effects of temporal sampling, glucose metabolic rates, and disruptions of the blood-brain barrier on the FDG model with and without a vascular compartment: studies in human brain tumors with PET.

The addition of a cerebral blood volume (CBV) compartment in the [18F]2-fluoro-2-deoxy-D-glucose (FDG) model produces estimates of local CBV simultaneously with glucose metabolic rates when kinetic FDG studies are performed. We investigated the influence of this term upon CMRglc values in a series of brain tumor patients and found that significant overestimations of CMRglc are possible if the effect of CBV upon the model is ignored. The magnitude of this potential overestimation is directly related to the absolute value of CBV locally and inversely related to the CMRglc value. The kinetic estimates also permitted an evaluation of the FDG model in an environment with a variable disruption of the blood-brain barrier. Incorporating the vascular compartment in the FDG model also frequently improved the statistical accuracy of model fits to tissue kinetic data. The sampling requirements for this model configuration were also investigated in a series of computer simulations.

KINETIC STUDIES OF HUMAN BRAIN TUMORS WITH POSITRON COMPUTED TOMOGRAPHY (PCT)

We studied 9 patients with primary and metastatic brain tumors with PCT. All subjects had kinetic F-18 fluorodeoxyglucose (FDG) studies. A modified version of the FDG model permitted estimates of the rate constants k1*, k2*, k3* and k4* as well as a fifth parameter representing cerebral blood volume (CBV). 6 subjects had CBF studies with 0–15 water, 4 subjects had CBV studies with 0–15 CO and 3 subjects had BBB kinetic studies the Ga-68 EDTA. Estimated values of CBV determined kinetically with FDG averaged 6.09 (± 1.35)cc/100gm in tumors compared to 7.47 (± 2.60)cc/100gm measured directly with 0–15 CO. The ratio of the relative CBV (determined kinetically with FDG versus directly with CO) in gray matter and tumors (compared to global values) averaged 1.02 (± 0.18) in these same 4 subjects. Simulation studies on the impact of CBV upon glucose metabolic rates (CMRG1c) determined with FDG indicated a larger overestimation of CMRG1c as CBV increased. The estimated CMRG1c determined with and without a CBV correction approached the same value in the actual patient studies as CBV decreased, in agreement with the simulation results. CBF and CMRG1c measurements together permitted calculation of net glucose extraction (GER). We found an inverse relationship between CBF and GER. Quantitative estimates of BBB permeability demonstrated no dramatic change in FDG rate constants as a function of BBB permeability changes. These studies indicate: 1) kinetic estimates of CBV in tumor and normal tissue is possible with FDG and 2) the relationships between CBF, GER and BBB permeability is quantifiable in human tumors with PCT.