Estimates Of Cerebral Blood Volume Research Articles

Contrast-free dynamic susceptibility contrast using sinusoidal and bolus oxygenation challenges.

Deoxygenation-based dynamic susceptibility contrast (dDSC) MRI uses respiratory challenges as a source of endogenous contrast as an alternative to gadolinium injection. These gas challenges induce T2*-weighted MRI signal losses, after which tracer kinetics modeling was applied to calculate cerebral perfusion. This work compares three gas challenges, desaturation (transient hypoxia), resaturation (transient normoxia), and SineO2 (sinusoidal modulation of end-tidal oxygen pressures) in a cohort of 10 healthy volunteers (age 37 ± 11 years; 60% female). Perfusion estimates consisted of cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT). Calculations were computed using a traditional tracer kinetics model in the time domain for desaturation and resaturation and in the frequency domain for SineO2. High correlations and limits of agreement were observed among the three deoxygenation-based paradigms for CBV, although MTT and CBF estimates varied with the hypoxic stimulus. Cross-modality correlation with gadolinium DSC was lower, particularly for MTT, but on a par with agreement between the other perfusion references. Overall, this work demonstrated the feasibility and reliability of oxygen respiratory challenges to measure brain perfusion. Additional work is needed to assess the utility of dDSC in the diagnostic evaluation of various pathologies such as ischemic strokes, brain tumors, and neurodegenerative diseases.

Probing the glioma microvasculature: a case series of the comparison between perfusion MRI and intraoperative high-frame-rate ultrafast Doppler ultrasound

BackgroundWe aimed to describe the microvascular features of three types of adult-type diffuse glioma by comparing dynamic susceptibility contrast (DSC) perfusion magnetic resonance imaging (MRI) with intraoperative high-frame-rate ultrafast Doppler ultrasound.MethodsCase series of seven patients with primary brain tumours underwent both DSC perfusion MRI and intra-operative high-frame-rate ultrafast Doppler ultrasound. From the ultrasound images, three-dimensional vessel segmentation was obtained of the tumour vascular bed. Relative cerebral blood volume (rCBV) maps were generated with leakage correction and normalised to the contralateral normal-appearing white matter. From tumour histograms, median, mean, and maximum rCBV ratios were extracted.ResultsLow-grade gliomas (LGGs) showed lower perfusion than high-grade gliomas (HGGs), as expected. Within the LGG subgroup, oligodendroglioma showed higher perfusion than astrocytoma. In HGG, the median rCBV ratio for glioblastoma was 3.1 while astrocytoma grade 4 showed low perfusion with a median rCBV of 1.2. On the high-frame-rate ultrafast Doppler ultrasound images, all tumours showed a range of rich and organised vascular networks with visually apparent abnormal vessels, even in LGG.ConclusionsThis unique case series revealed in vivo insights about the microvascular architecture in both LGGs and HGGs. Ultrafast Doppler ultrasound revealed rich vascularisation, also in tumours with low perfusion at DSC MRI. These findings warrant further investigations using advanced MRI postprocessing, in particular for characterising adult-type diffuse glioma.Relevance statementOur findings challenge the current assumption behind the estimation of relative cerebral blood volume that the distribution of blood vessels in a voxel is random.Key points• Ultrafast Doppler ultrasound revealed rich vascularity irrespective of perfusion dynamic susceptibility contrast MRI state.• Rich and organised vascularisation was also observed even in low-grade glioma.• These findings challenge the assumptions for cerebral blood volume estimation with MRI.Graphical

Longitudinal Assessment of Cerebral Blood Volume Variation in Human Neonates Using Ultrafast Power Doppler and Diverging Waves

Longitudinal assessment of brain perfusion is a critical parameter for neurodevelopmental outcome of neonates undergoing cardiopulmonary bypass procedure. In this study, we aim to measure the variations of cerebral blood volume (CBV) in human neonates during cardiac surgery, using Ultrafast Power Doppler and freehand scanning. To be clinically relevant, this method must satisfy three criteria: being able to image a wide field of view in the brain, show significant longitudinal CBV variations, and present reproducible results. To address the first point, we performed for the first time transfontanellar Ultrafast Power Doppler using a hand-held phased-array transducer with diverging waves. This increased the field of view more than threefold compared to previous studies using linear transducers and plane waves. We were able to image vessels in the cortical areas as well as the deep grey matter and temporal lobes. Second, we measured the longitudinal variations of CBV on human neonates undergoing cardiopulmonary bypass. When compared to a pre-operative baseline acquisition, the CBV exhibited significant variation during bypass: on average, +20±3% in the mid-sagittal full sector (p<0.0001), -11±3% in the cortical regions (p<0.01) and -10±4% in the basal ganglia (p<0.01). Third, a trained operator performing identical scans was able to reproduce CBV estimates with a variability of 4% to 7.5% depending on the regions considered. We also investigated whether vessel segmentation could further improve reproducibility, but found that it actually introduced greater variability in the results. Overall, this study demonstrates the clinical translation of ultrafast power Doppler with diverging-waves and freehand scanning.

Three-dimensional whole-brain mapping of cerebral blood volume and venous cerebral blood volume using Fourier transform-based velocity-selective pulse trains.

To develop 3D MRI methods for cerebral blood volume (CBV) and venous cerebral blood volume (vCBV) estimation with whole-brain coverage using Fourier transform-based velocity-selective (FT-VS) pulse trains. For CBV measurement, FT-VS saturation pulse trains were used to suppress static tissue, whereas CSF contamination was corrected voxel-by-voxel using a multi-readout acquisition and a fast CSF T2 scan. The vCBV mapping was achieved by inserting an arterial-nulling module that included a FT-VS inversion pulse train. Using these methods, CBV and vCBV maps were obtained on 6 healthy volunteers at 3 T. The mean CBV and vCBV values in gray matter and white matter in different areas of the brain showed high correlation (r = 0.95 and P < .0001). The averaged CBV and vCBV values of the whole brain were 5.4 ± 0.6 mL/100 g and 2.5 ± 0.3 mL/100 g in gray matter, and 2.6 ± 0.5 mL/100 g and 1.5 ± 0.2 mL/100 g in white matter, respectively, comparable to the literature. The feasibility of FT-VS-based CBV and vCBV estimation was demonstrated for 3D acquisition with large spatial coverage.

The impact of EPI-based distortion correction of dynamic susceptibility contrast MRI on cerebral blood volume estimation in patients with glioblastoma

PurposeRelative cerebral blood volume (rCBV) from dynamic susceptibility contrast (DSC)-MRI is a valuable biomarker in patients with glioblastoma for assessing treatment response and predicting overall survival. DSC-MRI based on echo planar images (EPI) may possess severe geometric distortions from magnetic field inhomogeneities up to the order of centimeters. The aim of this study is to assess how much two readily available EPI-based geometric distortion correction methods, FSL TOPUP and EPIC, affect rCBV values from DSC-MRI in patients with confirmed glioblastoma. MethodWe used a combined single-shot 2D gradient-echo (T2*), spin-echo (T2) EPI sequence to estimate both T2* and T2-weighted rCBV from the same contrast agent injection. Effects of distortion correction on the positive phase-encoded T2- and T2*-images were assessed in healthy anatomical brain regions in terms of Wilcoxon signed rank tests on median rCBV change and on Dice coefficients, as well as in tumor lesions in terms of Wilcoxon signed rank tests on median rCBV change. ResultsOur results show that following distortion correction, both gradient-echo and spin-echo rCBV increased in cortical areas of the frontal, temporal and occipital lobe, including the posterior orbital gyri in the frontal lobe and middle frontal gyri (p < 0.0008). Similar, improved Dice coefficients were observed for gradient-echo EPI in temporal, occipital and frontal lobe. Only spin-echo rCBV in enhancing lesion increased with correction (p = 0.0002). ConclusionOur study sheds light on the importance of performing geometric distortion correction on EPI-based MRI data before assessing functional information such as rCBV values. Our findings may indicate that uncorrected rCBV values can be underestimated from positive phase-encoding EPI and that geometric distortion correction is warranted when comparing EPI-based data to conventional MRI.

Consensus recommendations for a dynamic susceptibility contrast MRI protocol for use in high-grade gliomas.

Despite the widespread clinical use of dynamic susceptibility contrast (DSC) MRI, DSC-MRI methodology has not been standardized, hindering its utilization for response assessment in multicenter trials. Recently, the DSC-MRI Standardization Subcommittee of the Jumpstarting Brain Tumor Drug Development Coalition issued an updated consensus DSC-MRI protocol compatible with the standardized brain tumor imaging protocol (BTIP) for high-grade gliomas that is increasingly used in the clinical setting and is the default MRI protocol for the National Clinical Trials Network. After reviewing the basis for controversy over DSC-MRI protocols, this paper provides evidence-based best practices for clinical DSC-MRI as determined by the Committee, including pulse sequence (gradient echo vs spin echo), BTIP-compliant contrast agent dosing (preload and bolus), flip angle (FA), echo time (TE), and post-processing leakage correction. In summary, full-dose preload, full-dose bolus dosing using intermediate (60°) FA and field strength-dependent TE (40-50 ms at 1.5 T, 20-35 ms at 3 T) provides overall best accuracy and precision for cerebral blood volume estimates. When single-dose contrast agent usage is desired, no-preload, full-dose bolus dosing using low FA (30°) and field strength-dependent TE provides excellent performance, with reduced contrast agent usage and elimination of potential systematic errors introduced by variations in preload dose and incubation time.

Exploring Two Methods of CBV Estimation in Two Groups of Grade III Gliomas with Different Appearance on Post-Contrast T1 Images.

Background: Many studies have used Cerebral Blood Volume (CBV) for gliomas grading and there has been in good agreement between CBV and tumor grade. Almost all of those studies have emphasized the importance of leakage correction due to the underestimation/overestimation of CBV caused by T1/T2* leakage effect in enhanced cases of tumors, especially high grade ones.Objectives: The aim of this study is to investigate two methods of CBV estimation in two groups of gliomas with the same grade and different appearance on post contrast T1 images (Enhanced vs. Non-enhanced ones).Material and Methods: In this retrospective study, eight glioma patients with histopatologically confirmed grade III were equally divided into two groups (with enhancement (group 1) and without enhancement (group 2)), and retrospectively studied. Imaging was performed on a 3 tesla MR Scanner and included gradient-echo DSC, 3D T1-weighted dataset and FLAIR images. The conventional method of CBV measurement (Integration over the whole curve of CTC- method 1) and the GVF fitting (method 2) was done using Matlab. Results: The observed mean rCBV in the tumor ROI was 2.85 and 2.12 for group 1 with method 1 and 2, respectively. Mean rCBV in the tumor ROI for group 2 was 1.24 and 1.11 with method 1 and 2, respectively.Conclusion: In conclusion, this pilot study demonstrated that with combined use of pre-bolus and accounting for T2* effect, CBV could be considered as a criterion for the categorization of glioma tumors.

Measurements of cerebral blood volume using quantitative susceptibility mapping, R2 * relaxometry, and ferumoxytol-enhanced MRI.

Ferumoxytol-enhanced MRI holds potential for the non-invasive assessment of vascular architecture using estimates of cerebral blood volume (CBV). Ferumoxytol specifically enables steady-state imaging with extended acquisition times, for substantial improvements in resolution and contrast-to-noise ratio. With such data, quantitative susceptibility mapping (QSM) can be used to obtain images of local tissue magnetic susceptibility and hence estimate the increase in blood susceptibility after administration of a contrast agent, which in turn can be correlated to tissue CBV. Here, we explore the use of QSM for CBV estimation and compare it with R2 * (1/T2 *)-based results. Institutional review board approval was obtained, and all subjects provided written informed consent. For this prospective study, MR images were acquired on a 3.0T scanner in 19 healthy subjects using a multiple-echo T2 *-weighted sequence. Scanning was performed before and after the administration of two doses of ferumoxytol (1mg FE/kg and 4mg FE/kg). Different QSM approaches were tested on numerical phantom simulations. Results showed that the accuracy of magnetic susceptibility measurements improved with increasing image resolution and decreasing vascular density. In vivo changes in magnetic susceptibility were measured after the administration of ferumoxytol utilizing QSM, and significantly higher QSM-based CBV was measured in gray matter compared with white matter. QSM- and R2 *-based CBV estimates correlated well, with similar average values, but a larger variance was found in QSM-based estimates.

MRI Relaxometry for Quantitative Analysis of USPIO Uptake in Cerebral Small Vessel Disease.

A protocol for evaluating ultrasmall superparamagnetic particles of iron oxide (USPIO) uptake and elimination in cerebral small vessel disease patients was developed and piloted. B1-insensitive R1 measurement was evaluated in vitro. Twelve participants with history of minor stroke were scanned at 3-T MRI including structural imaging, and R1 and R2* mapping. Participants were scanned (i) before and (ii) after USPIO (ferumoxytol) infusion, and again at (iii) 24–30 h and (iv) one month. Absolute and blood-normalised changes in R1 and R2* were measured in white matter (WM), deep grey matter (GM), white matter hyperintensity (WMH) and stroke lesion regions. R1 measurements were accurate across a wide range of values. R1 (p < 0.05) and R2* (p < 0.01) mapping detected increases in relaxation rate in all tissues immediately post-USPIO and at 24–30 h. R2* returned to baseline at one month. Blood-normalised R1 and R2* changes post-infusion and at 24–30 h were similar, and were greater in GM versus WM (p < 0.001). Narrower distributions were seen with R2* than for R1 mapping. R1 and R2* changes were correlated at 24–30 h (p < 0.01). MRI relaxometry permits quantitative evaluation of USPIO uptake; R2* appears to be more sensitive to USPIO than R1. Our data are explained by intravascular uptake alone, yielding estimates of cerebral blood volume, and did not support parenchymal uptake. Ferumoxytol appears to be eliminated at 1 month. The approach should be valuable in future studies to quantify both blood-pool USPIO and parenchymal uptake associated with inflammatory cells or blood-brain barrier leak.

Simultaneous perfusion and permeability assessments using multiband multi‐echo EPI (M2‐EPI) in brain tumors

To study a multiband multi-echo EPI (M2-EPI) sequence for dynamic susceptibility contrast (DSC) perfusion imaging with leakage correction and vascular permeability measurements, and to evaluate the benefits of increased temporal resolution provided by this acquisition strategy on the accuracy of perfusion and permeability estimations. A novel M2-EPI sequence was developed, and a pharmacokinetic model accounting for contrast agent extravasation was used to produce perfusion maps and additional vascular permeability maps. The advantage of M2-EPI for DSC perfusion imaging was demonstrated in vivo in 5 patients with brain tumors, and numerical simulations were performed to evaluate the advantage of improved temporal resolution afforded by the technique. In contrast to underestimations of cerebral blood volume (CBV) in tumors using the single-echo acquisition strategy, M2-EPI provided more plausible estimates of CBV. A quantitative evaluation showed higher estimated values of CBV and mean transit time in tumor tissues using M2-EPI (CBV: 3.08 ± 0.78 mL/100 g versus 1.56 ± 1.38 mL/100 g [P = .006]; mean transit time: 4.94 ± 1.17 seconds versus 1.83 ± 2.06 seconds [P = 0.033]). Numerical simulations showed that higher temporal resolution provided by M2-EPI was associated with more accurate estimates of cerebral blood flow, CBV, and permeability parameters. The novel M2-EPI acquisition strategy for DSC imaging facilitates leakage-corrected perfusion measurements with additional permeability assessments and more accurate estimates of perfusion/permeability parameters, and may be used as a quantitative tool for the diagnosis, prognosis, and treatment monitoring of brain tumors.

Comparison of ferumoxytol‐based cerebral blood volume estimates using quantitative R1 and relaxometry

Cerebral perfusion is commonly assessed clinically with dynamic susceptibility contrast MRI using a bolus injection of gadolinium-based contrast agents, resulting in semi-quantitative values of cerebral blood volume (CBV). Steady-state imaging with ferumoxytol allows estimation of CBV with the potential for higher precision and accuracy. Prior CBV studies have focused on the signal disrupting T2* effects, but ferumoxytol also has high signal-enhancing T1 relaxivity. The purpose of this study was to investigate and compare CBV estimation using T1 and T2*, with the goal of understanding the contrast mechanisms and quantitative differences. Changes in R1 (1/T1 ) and R2* (1/ T2*) were measured after the administration of ferumoxytol using high-resolution quantitative approaches. Images were acquired at 3.0T and R1 was estimated from an ultrashort echo time variable flip angle approach, while R2* was estimated from a multiple gradient echo sequence. Twenty healthy volunteers were imaged at two doses. CBV was derived and compared from relaxometry in gray and white matter using different approaches. R1 measurements showed a linear dependence of blood R1 with respect to dose in large vessels, in contrast to the nonlinear dose-dependence of blood R2* estimates. In the brain parenchyma, R2* showed linear dose-dependency whereas R1 showed nonlinearity. CBV calculations based on R2* changes in tissue and ferumoxytol blood concentration estimates based on R1 relaxivity showed the lowest variability in our cohort. CBV measurements were successfully derived using a combined approach of R1 and R2* relaxometry. Magn Reson Med 79:3072-3081, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Assessment of MRI contrast agent concentration by quantitative susceptibility mapping (QSM): application to estimation of cerebral blood volume during steady state

ObjectiveOne major issue in dynamic susceptibility contrast MRI (DSC-MRI) is to accurately determine contrast agent (CA) concentration, since T2* relaxivity in vivo is generally unknown and varies between blood and tissue. In this study, quantitative susceptibility mapping (QSM) was used for quantification of CA concentration.Materials and methodsA DSC-MRI protocol, including phase data acquisition, was applied to 20 healthy volunteers in a test–retest study. By selecting a CSF reference region of interest (ROI), the values of all QSM images were shifted to show no CA-induced change in CSF. CA concentration and cerebral blood volume (CBV) were estimated using shifted QSM data. CSF reference ROI optimization was evaluated by investigation of CBV repeatability. The CBV age dependence was analysed and tissue T2* relaxivity was estimated.ResultsThe best repeatability of CBV, using an optimal CSF reference ROI, showed test-versus-retest correlations of r = 0.81 and r = 0.91 for white and grey matter, respectively. A slight CBV decrease with age was observed, and the estimated in vivo T2* relaxivity was 85 mM−1s−1.ConclusionProvided that a carefully selected CSF reference ROI is used to shift QSM image values, susceptibility information can be used to estimate concentration of contrast agent and to calculate CBV.

Dynamic Susceptibility Contrast MRI at 7 T: Tail-Scaling Analysis and Inferences About Field Strength Dependence.

Dynamic susceptibility contrast magnetic resonance imaging (DSC-MRI) following bolus injection of gadolinium contrast agent (CA) is widely used for the estimation of brain perfusion parameters such as cerebral blood volume (CBV), cerebral blood flow (CBF), and mean transit time (MTT) for both clinical and research purposes. Although it is predicted that DSC-MRI will have superior performance at high magnetic field strengths, to the best of our knowledge, there are no reports of 7 T DSC-MRI in the literature. It is plausible that the transfer of DSC-MRI to 7 T may be accompanied by increased R2* relaxivity in tissue and a larger difference in ΔR2*-versus-concentration relationships between tissue and large vessels. If not accounted for, this will subsequently result in apparent CBV and CBF estimates that are higher than those reported previously at lower field strengths. The aims of this study were therefore to assess the feasibility of 7 T DSC-MRI and to investigate the apparent field-strength dependence of CBV and CBF estimates. In total, 8 healthy volunteers were examined using DSC-MRI at 7 T. A reduced CA dose of 0.05 mmol/kg was administered to decrease susceptibility artifacts. CBV, CBF, and MTT maps were calculated using standard DSC-MRI tracer-kinetic theory. Subject-specific arterial partial volume correction factors were obtained using a tail-scaling approach. Compared with literature values obtained using the tail-scaling approach at 1.5 T and 3 T, the CBV and CBF values of the present study were found to be further overestimated. This observation is potentially related to an inferred field-strength dependence of transverse relaxivities, although issues related to the CA dose must also be considered.

Bidirectional Contrast agent leakage correction of dynamic susceptibility contrast (DSC)-MRI improves cerebral blood volume estimation and survival prediction in recurrent glioblastoma treated with bevacizumab.

To evaluate a leakage correction algorithm for T1 and T2* artifacts arising from contrast agent extravasation in dynamic susceptibility contrast magnetic resonance imaging (DSC-MRI) that accounts for bidirectional contrast agent flux and compare relative cerebral blood volume (CBV) estimates and overall survival (OS) stratification from this model to those made with the unidirectional and uncorrected models in patients with recurrent glioblastoma (GBM). We determined median rCBV within contrast-enhancing tumor before and after bevacizumab treatment in patients (75 scans on 1.5T, 19 scans on 3.0T) with recurrent GBM without leakage correction and with application of the unidirectional and bidirectional leakage correction algorithms to determine whether rCBV stratifies OS. Decreased post-bevacizumab rCBV from baseline using the bidirectional leakage correction algorithm significantly correlated with longer OS (Cox, P = 0.01), whereas rCBV change using the unidirectional model (P = 0.43) or the uncorrected rCBV values (P = 0.28) did not. Estimates of rCBV computed with the two leakage correction algorithms differed on average by 14.9%. Accounting for T1 and T2* leakage contamination in DSC-MRI using a two-compartment, bidirectional rather than unidirectional exchange model might improve post-bevacizumab survival stratification in patients with recurrent GBM. J. Magn. Reson. Imaging 2016;44:1229-1237.

Cerebral blood volume estimation by ferumoxytol-enhanced steady-state MRI at 9.4 T reveals microvascular impact of α1 -adrenergic receptor antibodies.

Cerebrovascular abnormality is frequently accompanied by cognitive dysfunctions, such as dementia. Antibodies against the α1 -adrenoceptor (α1 -AR) can be found in patients with Alzheimer's disease with cerebrovascular disease, and have been shown to affect the larger vessels of the brain in rodents. However, the impact of α1 -AR antibodies on the cerebral vasculature remains unclear. In the present study, we established a neuroimaging method to measure the relative cerebral blood volume (rCBV) in small rodents with the ultimate goal to detect changes in blood vessel density and/or vessel size induced by α1 -AR antibodies. For this purpose, mapping of R2 * and R2 was performed using MRI at 9.4 T, before and after the injection of intravascular iron oxide particles (ferumoxytol). The change in the transverse relaxation rates (ΔR2 *, ΔR2 ) showed a significant rCBV decrease in the cerebrum, cortex and hippocampus of rats (except hippocampal ΔR2 ), which was more pronounced for ΔR2 * than for ΔR2 . Immunohistological analyses confirmed that the α1 -AR antibody induced blood vessel deficiencies. Our findings support the hypothesis that α1 -AR antibodies lead to cerebral vessel damage throughout the brain, which can be monitored by MRI-derived rCBV, a non-invasive neuroimaging method. This demonstrates the value of rCBV estimation by ferumoxytol-enhanced MRI at 9.4 T, and further underlines the significance of this antibody in brain diseases involving vasculature impairments, such as dementia.

Dynamic susceptibility contrast MRI with a prebolus contrast agent administration design for improved absolute quantification of perfusion

Arterial partial-volume effects (PVEs) often hamper reproducible absolute quantification of cerebral blood flow (CBF) and cerebral blood volume (CBV) obtained by dynamic susceptibility contrast MRI (DSC-MRI). The aim of this study was to examine whether arterial PVEs in DSC-MRI data can be minimized by rescaling the arterial input function (AIF) using a sagittal-sinus venous output function obtained following a prebolus administration of a low dose of contrast agent. The study was carried out as a test-retest experiment in 20 healthy volunteers to examine the repeatability of the CBF and CBV estimates. All subjects were scanned twice with 7-20 days between investigations. DSC-MRI returned an overestimated average whole-brain CBF of 220 ± 44 mL/100 g/min (mean ± SD) before correction and 44 ± 15 mL/100 g/min when applying the prebolus design, averaged over all scans. Average whole-brain CBV was 20 ± 2.0 mL/100 g before correction and 4.0 ± 1.0 mL/100 g after prebolus correction. Quantitative estimates of CBF and CBV, obtained with the proposed prebolus DSC-MRI technique, approached those typically obtained by other perfusion modalities. The CBF and CBV estimates showed good repeatability.

Noninvasive MRI measurement of the absolute cerebral blood volume–cerebral blood flow relationship during visual stimulation in healthy humans

The relationship between cerebral blood volume (CBV) and cerebral blood flow (CBF) underlies blood oxygenation level-dependent functional MRI signal. This study investigates the potential for improved characterization of the CBV-CBF relationship in humans, and examines sex effects as well as spatial variations in the CBV-CBF relationship. Healthy subjects were imaged noninvasively at rest and during visual stimulation, constituting the first MRI measurement of the absolute CBV-CBF relationship in humans with complete coverage of the functional areas of interest. CBV and CBF estimates were consistent with the literature, and their relationship varied both spatially and with sex. In a region of interest with stimulus-induced activation in CBV and CBF at a significance level of the P < 0.05, a power function fit resulted in CBV = 2.1 CBF(0.32) across all subjects, CBV = 0.8 CBF(0.51) in females and CBV = 4.4 CBF(0.15) in males. Exponents decreased in both sexes as ROIs were expanded to include less significantly activated regions. Consideration for potential sex-related differences, as well as regional variations under a range of physiological states, may reconcile some of the variation across literature and advance our understanding of the underlying cerebrovascular physiology.

Pre- and post-contrast three-dimensional double inversion-recovery MRI in human glioblastoma

Fluid attenuated inversion recovery (FLAIR) MRI sequences have become an indispensible tool for defining the malignant boundary in patients with brain tumors by nulling the signal contribution from cerebrospinal fluid allowing both regions of edema and regions of non-enhancing, infiltrating tumor to become hyperintense on resulting images. In the current study we examined the utility of a three-dimensional double inversion recovery (DIR) sequence that additionally nulls the MR signal associated with white matter, implemented either pre-contrast or post-contrast, in order to determine whether this sequence allows for better differentiation between tumor and normal brain tissue. T1- and T2-weighted, FLAIR, dynamic susceptibility contrast (DSC)-MRI estimates of cerebral blood volume (rCBV), contrast-enhanced T1-weighted images (T1+C), and DIR data (pre- or post-contrast) were acquired in 22 patients with glioblastoma. Contrast-to-noise (CNR) and tumor volumes were compared between DIR and FLAIR sequences. Line profiles across regions of tumor were generated to evaluate similarities between image contrasts. Additionally, voxel-wise associations between DIR and other sequences were examined. Results suggested post-contrast DIR images were hyperintense (bright) in regions spatially similar those having FLAIR hyperintensity and hypointense (dark) in regions with contrast-enhancement or elevated rCBV due to the high sensitivity of 3D turbo spin echo sequences to susceptibility differences between different tissues. DIR tumor volumes were statistically smaller than tumor volumes as defined by FLAIR (Paired t test, P = 0.0084), averaging a difference of approximately 14 mL or 24 %. DIR images had approximately 1.5× higher lesion CNR compared with FLAIR images (Paired t test, P = 0.0048). Line profiles across tumor regions and scatter plots of voxel-wise coherence between different contrasts confirmed a positive correlation between DIR and FLAIR signal intensity and a negative correlation between DIR and both post-contrast T1-weighted image signal intensity and rCBV. Additional discrepancies between FLAIR and DIR abnormal regions were also observed, together suggesting DIR may provide additional information beyond that of FLAIR.

Simultaneous Perfusion and Permeability Measurements Using Combined Spin- and Gradient-Echo MRI

The purpose of this study was to estimate magnetic resonance imaging-based brain perfusion parameters from combined multiecho spin-echo and gradient-echo acquisitions, to correct them for T₁₋, T₂₋, and T₂₋*-related contrast agent (CA) extravasation effects, and to simultaneously determine vascular permeability. Perfusion data were acquired using a combined multiecho spin- and gradient-echo (SAGE) echo-planar imaging sequence, which was corrected for CA extravasation effects using pharmacokinetic modeling. The presented method was validated in simulations and brain tumor patients, and compared with uncorrected single-echo and multiecho data. In the presence of CA extravasation, uncorrected single-echo data resulted in underestimated CA concentrations, leading to underestimated single-echo cerebral blood volume (CBV) and mean transit time (MTT). In contrast, uncorrected multiecho data resulted in overestimations of CA concentrations, CBV, and MTT. The correction of CA extravasation effects resulted in CBV and MTT estimates that were more consistent with the underlying tissue characteristics. Spin-echo perfusion data showed reduced large-vessel blooming effects, facilitating better distinction between increased CBV due to active tumor progression and elevated CBV due to the presence of cortical vessels in tumor proximity. Furthermore, extracted permeability parameters were in good agreement with elevated T1-weighted postcontrast signal values.

The Role of Preload and Leakage Correction in Gadolinium-Based Cerebral Blood Volume Estimation Determined by Comparison with MION as a Criterion Standard

Contrast extravasation in DSC-MRI potentiates inaccurate and imprecise estimates of glioma rCBV. We tested assertions that preload and postprocessing algorithms minimize this error by comparing Gd-rCBV using permutations of these 2 techniques with criterion standard rCBV using MION, an intravascular agent. We imaged 7 Fisher rats with 9L gliosarcomas, by using 3T gradient-echo DSC-MRI with MION (2.0 mg Fe/kg) and staged injection of Gd-diethylene triamine pentaacetic acid: a 0.1-mmol/kg bolus provided no preload (P-) data and served as preload (P+) for a subsequent 0.2-mmol/kg bolus. We computed MION-rCBV (steady-state ΔR2*, tumor versus normal brain) and Gd-rCBV ΔR2* [t] integration) without (C-) and with (C+) postprocessing correction, thereby testing 4 correction permutations: P-C-, P-C+, P+C-, and P+C+. We tested whether each permutation reduced bias and variance of the Gd/MION rCBV differences by using generalized estimating equations and Fmax statistics (P < .05 significant). Gd-rCBV progressively better approximated MION-rCBV with increasing leakage correction. There was no statistically significant bias for the mean percentage deviation of Gd-rCBV from MION-rCBV for any correction permutation, but there was significantly reduced variance by using P+C- (22-fold), P-C+ (32-fold), and P+C+ (267-fold) compared with P-C-. P+C+ provided significant additional variance reduction compared with P+C- (12-fold) and P-C+ (8-fold). Linear regression of Gd-rCBV versus MION-rCBV revealed P+C+ to have the closest slope and intercept compared with the ideal, substantially better than P+C-. Preload and postprocessing correction significantly reduced the variance of Gd-rCBV estimates, and bias reduction approached significance. Postprocessing correction provide significant benefit beyond preload alone.