Inflow‐based vascular‐space‐occupancy (iVASO) MRI

Vascular‐space‐occupancy (VASO) MRI, a blood nulling approach for assessing changes in cerebral blood volume (CBV), is hampered by low signal‐to‐noise ratio (SNR) because only 10–20% of tissue signal is recovered when using nonselective inversion for blood nulling. A new approach, called inflow‐VASO (iVASO), is introduced in which only blood flowing into the slice has experienced inversion, thereby keeping tissue and cerebrospinal fluid (CSF) signal in the slice maximal and reducing CSF partial volume effects. SNR increases of 198% ± 12% and 334% ± 9% (mean ± SD, n = 7) with respect to VASO were found at TR values of 5s and 2s, respectively. When using inflow approaches, data interpretation is complicated by the fact that signal changes are affected by vascular transit times. An optimal TR‐range (1.5–2.5s) was derived in which the iVASO response during activation predominantly reflects arterial/arteriolar CBV (CBV_a) changes. In this TR‐range, perfusion contributions to the signal change are negligible because arterial label has not yet undergone capillary exchange, and arterial and precapillary blood signals are nulled. For TR = 2s, the iVASO signal change upon visual stimulation corresponded to a CBV_a increase of 58% ± 7%, in agreement with arteriolar CBV changes previously reported. The onset of the hemodynamic response for iVASO occurred 1.2 ± 0.5s (n = 7) faster than for conventional VASO. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.     

Measurement of regional blood oxygenation and cerebral hemodynamics

An echo planar linewidth mapping technique, Shufflebutt, has allowed temporal measurements of changes in linewidth caused by static inhomogeneities (ΔLWSI) and transverse relaxation rate (ΔR2) in models of hypoxia and hypercapnia. We demonstrate these changes are due to intravascular susceptibility differences(Δ_X) between the blood and tissue. Contrast agent injections at a /Δ_X equivalent to that of deoxygenatetd blood showed a twofold difference between the contrast agent and physiological anoxia values. Hypercapnia decreased both ΔLWSI and ΔR2 consistent with an increase in blood oxygenation. We attribute these findings to constant oxygen extraction during an increase in blood flow, resulting in less deoxygenated venous blood and thus reduced Δ_X. For in vivoperturbations we found that ΔR/ΔR2′ ≈ 0.33, a ratio much different from that measured in whole blood phantoms (ΔR/ΔR2′ ≈ 2). This demonstrates that signal changes in these studies are produced predominantly by dephasing of extravascular protons due to field inhomogeneities produced by intravascular deoxygenated hemoglobin (deoxyHb).     

Experimental measurement of extravascular parenchymal BOLD effects and tissue oxygen extraction fractions using multi‐echo VASO fMRI at 1.5 and 3.0 T

Quantitative interpretation of BOLD fMRI signal changes has predominantly employed empirical models for the whole parenchyma and a calibration step is usually needed to determine the physiological parameters during activation. Although analytical expressions are available for the extravascular and intravascular components of the BOLD effects, it is difficult to experimentally separate tissue from blood signal contributions at the low magnetic fields in which most fMRI studies are performed. Even if this can be achieved, an additional problem that remains is the separation of two types of extravascular BOLD effects, namely those around microvasculature (in the parenchyma close to the site of activation) and those around draining macrovasculature (e.g., in tissue and CSF more remote from the site of activation). In the recently developed vascular space occupancy technique, blood signals are nulled and the activations are localized predominantly in gray matter, allowing experimental measurement of parenchymal extravascular R₂* and its changes accompanying activation. When comparing such data with total parenchymal R₂* changes in BOLD fMRI, the extravascular fractions were found to be 47 ± 7% (mean ± SEM, n = 4) and 67 ± 6% at 1.5 and 3.0 T, respectively, in line with expectations that intravascular BOLD contributions are reduced at higher field. The present approach provides a noninvasive means to determine parenchymal oxygen extraction fraction (OEF) in situ. During visual stimulation, OEF values measured at 1.5 and 3.0 T were in good agreement, giving 0.23 ± 0.01 and 0.21 ± 0.01, respectively. Magn Reson Med 53:808–816, 2005. © 2005 Wiley‐Liss, Inc.     

Effects of acute normovolemic hemodilution on T2* - weighted images of rat brain

Acute normovolemic hernodilution (HD) was induced in anesthetized rats to assess the effect of changes in hematocrit (Hct) on signal intensity in T₂*-weighted magnetic resonance (MR) images. Other relevant physiological parameters were maintained invariant. Two degrees of HD were induced: mild (Hct reduced from 42.6 ± 2.2% to 33.4 ± 2.1%) and moderate (Hct reduced from 44.6 ± 2.7% to 26.2 ± 1.7%). A two-dimensional gradient-echo sequence was used to monitor signal changes with high temporal resolution before, during, and after HD protocols. The time course of signal intensity change was closely related to that of changes in Hct. Corresponding changes in R₂* (ΔR₂*) with respect to the pre-HD state were calculated for the brain parenchyma. Average ΔR₂* values of ?0.24 ± 0.06 s^?1 and ?0.40 ± 0.07 s^?1 were obtained for the mild and moderate HD groups, respectively, during the final 2 min of MR imaging (proximal to correlative measurements of Hct). MR measured ΔR₂* values were in close agreement with the expected changes in R₂* predicted from theory when the measured changes in Hct were used as independent variables. These data are in good agreement with the current understanding of the effects of changes in the intravascular concentration of deoxyhemoglobin on induced magnetic susceptibility and hold promise for quantitative measurement of brain oxygenation in vivo.     

Enhancement of gas‐filled microbubble R2* by iron oxide nanoparticles for MRI

Gas‐filled microbubbles have the potential to become a unique intravascular MR contrast agent due to their magnetic susceptibility effect, biocompatibility, and localized manipulation via ultrasound cavitation. However, microbubble susceptibility effect is relatively weak when compared with other intravascular MR susceptibility contrast agents. In this study, enhancement of microbubble susceptibility effect by entrapping monocrystalline iron oxide nanoparticles (MIONs) into polymeric microbubbles was investigated at 7 T in vitro. Apparent T₂ enhancement (ΔR₂*) induced by microbubbles was measured to be 79.2 ± 17.5 sec^?1 and 301.2 ± 16.8 sec^?1 for MION‐free and MION‐entrapped polymeric microbubbles at 5% volume fraction, respectively. ΔR₂* and apparent transverse relaxivities (r₂*) for MION‐entrapped polymeric microbubbles and MION‐entrapped solid microspheres (without gas core) were also compared, showing the synergistic effect of the gas core with MIONs. This is the first experimental demonstration of microbubble susceptibility enhancement for MRI application. This study indicates that gas‐filled polymeric microbubble susceptibility effect can be substantially increased by incorporating iron oxide nanoparticles into microbubble shells. With such an approach, microbubbles can potentially be visualized with higher sensitivity and lower concentrations by MRI. Magn Reson Med, 2010. © 2009 Wiley‐Liss, Inc.     

Reference region‐based pharmacokinetic modeling in quantitative dynamic contract‐enhanced MRI allows robust treatment monitoring in a rat liver tumor model despite cardiovascular changes

In this work, two pharmacokinetic modeling techniques, population arterial input function model, and reference region model, were applied to dynamic contract‐enhanced MRI data, to test the influence of a change in heart rate on modeling parameters. A rat population arterial input function was generated by dynamic contrast‐enhanced computed tomography measurements using the MR contrast agent gadolinium diethylenetriamine penta‐acetic acid. Then, dynamic contract‐enhanced MRI was used for treatment monitoring in two groups of hepatocellular carcinoma bearing rats. Whereas group 1 had the same heart rate as animals analyzed for the population arterial input function (263 ± 20 bpm), group 2 had a higher heart rate (369 ± 11 bpm) due to a different anesthesia protocol. The pharmacokinetic modeling parameters volume transfer constant K^trans and relative extravascular extracellular space v_e were calculated with both models and statistically compared. For group 1, good correlation and agreement was found between the models showing no difference in K^trans and v_e (ΔK^trans: 4 ± 19% and Δv_e: 4 ± 12%, P = 0.2). In contrast, for group 2, a bias in parameter values for the population arterial input function model was detected (ΔK^trans: ?45 ± 7% and Δv_e: ?31 ± 7%, P ≤ 0.001). The presented work underlines the value of the reference region model in longitudinal treatment monitoring and provides a straightforward approach for the generation of a rat population arterial input function. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.     

Experimental determination of the BOLD field strength dependence in vessels and tissue

High resolution functional MRI (fMRI) experiments were performed in human visual cortex at 0.5, 1.5, and 4 T to determine the blood oxygenation level dependent (BOLD) field strength response within regions of obvious venous vessels and cortical gray matter (“tissue”). T₂*-weighted FLASH images were collected in single- and multi-echo mode and used to determine the intrinsic BOLD parameters, namely, signal-to-noise ratio (Ψ), the apparent transverse relaxation rate (R₂*) and the change in R₂* (ΔR₂*) between the activated and baseline states. The authors find the average percentage signal change (ΔS/S, measured at TE = T₂*) to be large in vessels (13.3 ± 2.3%, 18.4 ± 4.0%, and 15.1 ± 1.2%) compared with that in tissue (1.4 ± 0.7%, 1.9 ± 0.7%, and 3.3 ± 0.2%) at 0.5, 1.5, and 4 T, respectively. The signal-to-noise ratio in optimized, fully relaxed proton density weighted gradient echo images was found to increase linearly with respect to the static magnetic field strength (B₀). The predicted upper bound on BOLD contrast-to-noise ratio (ΔS/R)_max as a function of field strength was calculated and found to behave less than linearly in voxels containing vessels larger than the voxel itself and greater than linearly in voxels containing a mixture of capillaries and veins/venules with a diameter less than that of the voxel.     

Effect of inflow of fresh blood on vascular‐space‐occupancy (VASO) contrast

In vascular‐space‐occupancy (VASO)‐MRI, cerebral blood volume (CBV)‐weighted contrast is generated by applying a nonselective inversion pulse followed by imaging when blood water magnetization is zero. An uncertainty in VASO relates to the completeness of blood water nulling. Specifically, radio frequency (RF) coils produce a finite inversion volume, rendering the possibility of fresh, non‐nulled blood. Here, VASO‐functional MRI (fMRI) was performed for varying inversion volume and TR using body coil RF transmission. For thin inversion volume thickness (δ_tot < 10 mm), VASO signal changes were positive (ΔS/S = 2.1–2.6%). Signal changes were negative and varied in magnitude for intermediate inversion volumes (δ_tot = 100–300 mm), yet did not differ significantly (P > 0.05) for δ_tot > 300 mm. These data suggest that blood water is in steady state for δ_tot > 300 mm. In this appropriate range, long‐TR VASO data converged to a less negative value (ΔS/S = –1.4% ± 0.2%) than short‐TR data (ΔS/S = –2.2% ± 0.2%), implying that cerebral blood flow or transit‐state effects may influence VASO contrast at short TR. Magn Reson Med 61:473–480, 2009. © 2009 Wiley‐Liss, Inc.     

Comparison of pulsed and pseudocontinuous arterial spin-labeling for measuring CO2 -induced cerebrovascular reactivity

Purpose:

To compare the performance of pulsed and pseudocontinuous arterial spin‐labeling (PASL and pCASL) methods in measuring CO₂‐induced cerebrovascular reactivity (CVR).

Materials and Methods:

Subjects were scanned using both ASL sequences during a controlled hypercapnia procedure and visual stimulation. CVR was computed as the percent CO₂‐induced increase in cerebral blood flow (Δ%CBF) per mmHg increase in end‐tidal PCO₂. Visually evoked responses were expressed as Δ%CBF. Resting CBF and temporal signal‐to‐noise ratio were also computed. Regionally averaged values for the different quantities were compared in gray matter (GM) and visual cortex (VC) using t‐tests.

Results:

Both PASL and pCASL yielded comparable respective values for resting CBF (56 ± 3 and 56 ± 4 mL/min/100g) and visually evoked responses (75 ± 5% and 81 ± 4%). Values of CVR determined using pCASL (GM 4.4 ± 0.2, VC 8 ± 1 Δ%CBF/mmHg), however, were significantly higher than those measured using PASL (GM 3.0 ± 0.6, VC 5 ± 1 Δ%CBF/mmHg) in both GM and VC. The percentage of GM voxels in which statistically significant hypercapnia responses were detected was also higher for pCASL (27 ± 5% vs. 16 ± 3% for PASL).

Conclusion:

pCASL may be less prone to underestimation of CO₂‐induced flow changes due to improved label timing control. J. Magn. Reson. Imaging 2012;36:312–321. © 2012 Wiley Periodicals, Inc.     

Quantification of venous vessel size in human brain in response to hypercapnia and hyperoxia using magnetic resonance imaging

Hypercapnia and hyperoxia give rise to vasodilation and vasoconstriction, respectively. This study investigates the influence of hypercapnia and hyperoxia on venous vessel size in the human brain. Venous vessel radii were measured in response to hypercapnia and hyperoxia. The venous vessel radii were determined by calculation of the changes in R₂* and R₂ that are induced by breathing 6% CO₂ or pure oxygen. The experimental paradigm consisted of two 3‐min intervals of inhaling 6% CO₂ or 100% O₂ interleaved with three 2‐min intervals of breathing air. Hypercapnic and hyperoxic experiments were performed on eight subjects on a 3T scanner. Parametric maps of mean venous vessel radius were calculated from the changes in R₂* and R₂, which were measured by simultaneous acquisition of gradient‐echo and spin‐echo signals. The mean venous vessel radii in hypercapnia were 7.3 ± 0.3 μm in gray matter and 6.6 ± 0.5 μm in white matter. The corresponding vessel radii in hyperoxia were 5.6 ± 0.2 μm in gray matter and 5.4 ± 0.2 μm in white matter. These results show that the venous vessel radius was larger in hypercapnia than that in hyperoxia in both gray matter and white matter (P < 0.005), which agrees with the hypothesis that hypercapnia causes vasodilation and hyperoxia induces vasoconstriction. Magn Reson Med, 2013. © 2012 Wiley Periodicals, Inc.     

Dynamic hysteresis between gradient echo and spin echo attenuations in dynamic susceptibility contrast imaging

Perfusion measurements using dynamic susceptibility contrast imaging provide additional information about the mean vessel size of microvasculature when supplemented with a dual gradient echo (GE) – spin echo (SE) contrast. Dynamic increase in the corresponding transverse relaxation rate constant changes, ΔR_2GE and ΔR_2SE, forms a loop on the (Δ, ΔR_2GE) plane, rather than a reversible line. The shape of the loop and the direction of its passage differentiate between healthy brain and pathological tissue, such as tumour and ischemic tissue. By considering a tree model of microvasculature, the direction of the loop is found to be influenced mainly by the relative arterial and venous blood volume, as well as the tracer bolus dispersion. A parameter Λ is proposed to characterize the direction and shape of the loop, which might be considered as a novel imaging marker for describing the pathology of cerebrovascular network. Magn Reson Med 69:981–991, 2013. © 2012 Wiley Periodicals, Inc.     

Bayesian estimation of changes in transverse relaxation rates

Although the biasing of R*₂ estimates by assuming magnitude MR data to be normally distributed has been described, the effect on changes in R*₂ (ΔR*₂), such as induced by a paramagnetic contrast agent, has not been reported. In this study, two versions of a novel Bayesian maximum a posteriori approach for estimating ΔR*₂ are described and evaluated: one that assumes normally distributed data and the other, Rice‐distributed data. The approach enables the robust, voxelwise determination of the uncertainty in ΔR*₂ estimates and provides a useful statistical framework for quantifying the probability that a pixel has been significantly enhanced. This technique was evaluated in vivo, using ultrasmall superparamagnetic iron oxide particles in orthotopic murine prostate tumors. It is shown that assuming magnitude data to be normally distributed causes ΔR*₂ to be underestimated when signal‐to‐noise ratio is modest. However, the biasing effect is less than is found in R*₂ estimates, implying that the simplifying assumption of normally distributed noise is more justifiable when evaluating ΔR*₂ compared with when evaluating precontrast R*₂ values. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.     

A two‐stage approach for measuring vascular water exchange and arterial transit time by diffusion‐weighted perfusion MRI

Changes in the exchange rate of water across the blood‐brain barrier, denoted k_w, may indicate blood‐brain barrier dysfunction before the leakage of large‐molecule contrast agents is observable. A previously proposed approach for measuring k_w is to use diffusion‐weighted arterial spin labeling to measure the vascular and tissue fractions of labeled water, because the vascular‐to‐tissue ratio is related to k_w. However, the accuracy of diffusion‐weighted arterial spin labeling is affected by arterial blood contributions and the arterial transit time (τ_a). To address these issues, a two‐stage method is proposed that uses combinations of diffusion‐weighted gradient strengths and post‐labeling delays to measure both τ_a and k_w. The feasibility of this method was assessed by acquiring diffusion‐weighted arterial spin labeling data from seven healthy volunteers. Repeat measurements and Monte Carlo simulations were conducted to determine the precision and accuracy of the k_w estimates. Average grey and white matter k_w values were 110 ± 18 and 126 ± 18 min^?1, respectively, which compare favorably to blood‐brain barrier permeability measurements obtained with positron emission tomography. The intrasubject coefficient of variation was 26% ± 23% in grey matter and 21% ± 17% in white matter, indicating that reproducible k_w measurements can be obtained. Magn Reson Med, 2012. © 2011 Wiley Periodicals, Inc.     

Experimental hypoxemic hypoxia: Changes in R2* of brain parenchyma accurately reflect the combined effects of changes in arterial and cerebral venous oxygen saturation

A two-dimensional T₂*-weighted gradient-echo sequence was used to image the rat brain before and during graded hypoxemia. Changes in R₂* (δR₂*) with respect to the control state were calculated for brain parenchyma and were compared with changes in hemoglobin saturation measured from both arterial and jugular venous blood samples. δR₂* was first correlated with the changes in arterial (δYa) and venous (δYv) hemoglobin saturations individually. Although a general trend toward a linear relationship with δR₂* was observed for both δYa and δYv, neither alone was strong (correlation coefficients r = 0.71 and 0.75 for δYa and δYv, respectively, and standard errors of the regression (SER) = 0.52 and 0.48 for δYa and δYv, respectively). However, when an “effective” cerebral blood hemoglobin saturation change (δYb) was constructed that takes into account the approximate weighting of the contributions from the arterial and venous phases of the circulation (δYb = 0.75 × δYv + 0.25 × δYa), a stronger correlation with δR₂* was obtained and there was less variance (r = 0.87 and SER = 0.35). It is concluded that an appropriate weighting of the contributions of arterial and venous phases of the circulation must be taken into account in modeling the volume susceptibility effects of deoxyhemoglobin on R₂* of brain parenchyma. In this way, a more accurate relationship between δR₂* and δYb can be obtained.     

Dynamic and simultaneous MR measurement of R1 and R2* changes during respiratory challenges for the assessment of blood and tissue oxygenation

This work presents a novel method for the rapid and simultaneous measurement of R₁ and R₂* relaxation rates. It is based on a dynamic short repetition time steady‐state spoiled multigradient‐echo sequence and baseline R₁ and B₁ measurements. The accuracy of the approach was evaluated in simulations and a phantom experiment. The sensitivity and specificity of the method were demonstrated in one volunteer and in four patients with intracranial tumors during carbogen inhalation. We utilized (ΔR₂*, ΔR₁) scatter plots to analyze the multiparametric response amplitude of each voxel within an area of interest. In normal tissue R₂* decreased and R₁ increased moderately in response to the elevated blood and tissue oxygenation. A strong negative ΔR₂* and ΔR₁ response was observed in veins and some tumor areas. Moderate positive ΔR₂* and ΔR₁ response amplitudes were found in fluid‐rich tissue as in cerebrospinal fluid, peritumoral edema, and necrotic areas. The multiparametric approach was shown to increase the specificity and sensitivity of oxygen‐enhanced MRI compared to measuring ΔR₂* or ΔR₁ alone. It is thus expected to provide an optimal tool for the identification of tissue areas with low oxygenation, e.g., in tumors with compromised oxygen supply. Magn Reson Med, 2013. © 2012 Wiley Periodicals, Inc.     

Estimating cerebral blood volume with expanded vascular space occupancy slice coverage

A model for quantifying cerebral blood volume (CBV) based on the vascular space occupancy (VASO) technique and varying the extent of blood nulling yielding task‐related signal changes with various amounts of blood oxygenation level‐dependent (BOLD) and VASO weightings was previously described. Challenges associated with VASO include limited slice coverage and the confounding inflow of fresh blood. In this work, an approach that extends the previous model to multiple slices and accounts for the inflow effect is described and applied to data from a multiecho sequence simultaneously acquiring VASO, cerebral blood flow (CBF), and BOLD images. This method led to CBV values (7.9 ± 0.3 and 5.6 ± 0.3 ml blood/100 ml brain during activation [CBV_ACT] and rest [CBV_REST], respectively) consistent with previous studies using similar visual stimuli. Furthermore, an increase in effective blood relaxation (0.65 ± 0.01) compared to the published value (0.62) was detected, likely reflecting inflow of fresh blood. Finally, cerebral metabolic rate of oxygen (CMRO₂) estimates using a multiple compartment model without assumption of CBV_REST led to estimates (18.7 ± 17.0%) that were within published ranges. Magn Reson Med, 2009. © 2009 Wiley‐Liss, Inc.     

Absence of a significant extravascular contribution to the skeletal muscle BOLD effect at 3 T

Blood oxygenation level dependent (BOLD) contrast in skeletal may reflect the contributions of both intravascular and extravascular relaxation effects. The purpose of this study was to determine the significance of the extravascular BOLD effect in skeletal muscle at 3 T. In experiments, R₂* was measured before and during arterial occlusion under the following conditions: ( 1 ) the leg extended and rotated (to vary the capillary orientation with respect to the amplitude of static field) and ( 2 ) with the blood's signal nulled using a multiecho vascular space occupancy experiment. In the leg rotation protocol, 3 min of arterial occlusion decreased oxyhemoglobin saturation from 67% to 45% and increased R₂* from 34.2 to 36.6 sec^?1, but there was no difference in the R₂* response to occlusion between the extended and rotated positions. Numerical simulations of intra‐ and extravascular BOLD effects corresponding to these conditions predicted that the intravascular BOLD contribution to the R₂* change was always > 50 times larger than the extravascular BOLD contribution. Blood signal nulling eliminated the change in R₂* caused by arterial occlusion. These data indicate that under these experimental conditions, the contribution of the extravascular BOLD effect to skeletal muscle R₂* was too small to be practically important. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.     

Phase contrast MRI quantification of pulsatile volumes of brain arteries, veins, and cerebrospinal fluids compartments: repeatability and physiological interactions

Purpose:

To study measurement repeatability and physiological determinants on measurement stability for phase contrast MRI (PC‐MRI) measurements of cyclic volume changes (ΔV) of brain arteries, veins, and cerebrospinal fluid (CSF) compartments.

Materials and Methods:

Total cerebral blood flow (tCBF), total internal jugular flow (tJBF) and spinal CSF flow at C2–C3 level and CSF in the aqueduct was measured using five repetitions in 20 healthy subjects. After subtracting net flow, waveforms were integrated to calculate ΔV of arterial, venous, and cerebrospinal fluid compartments. The intraclass correlation coefficient (ICC) was used to measure repeatability. Systematic errors were investigated by a series of phantom measurements.

Results:

For ΔV calculated from tCBF, tJBF and both CSF waveforms, the ICC was ≥0.85. ΔV from the tCBF waveform decreased linearly between repetitions (P = 0.012). Summed CSF and venous volume being shifted out from the cranium was correlated with ΔV calculated from the tCBF waveform (r = 0.75; P < 0.001). Systematic errors increased at resolutions <4 pixels per diameter.

Conclusion:

Repeatability of ΔV calculated from tCBF, tJBF, and CSF waveforms allows useful interpretations. The subject's time in the MR system and imaging resolution should be considered when interpreting volume changes. Summed CSF and venous volume changes was associated with arterial volume changes. J. Magn. Reson. Imaging 2012;35:1055‐1062. © 2011 Wiley Periodicals, Inc.     

The MRI‐measured arterial input function resulting from a bolus injection of Gd‐DTPA in a rat model of stroke slightly underestimates that of Gd‐[14C]DTPA and marginally overestimates the blood‐to‐brain influx rate constant determined by Patlak plots

The hypothesis that the arterial input function (AIF) of gadolinium‐diethylenetriaminepentaacetic acid injected by intravenous bolus and measured by the change in the T₁‐relaxation rate (ΔR₁; R₁ = 1/T₁) of superior sagittal sinus blood (AIF‐I) approximates the AIF of ¹⁴C‐labeled gadolinium‐diethylenetriaminepentaacetic acid measured in arterial blood (reference AIF) was tested in a rat stroke model (n = 13). Contrary to the hypothesis, the initial part of the ΔR₁‐time curve was underestimated, and the area under the normalized curve for AIF‐I was about 15% lower than that for the reference AIF. Hypothetical AIFs for gadolinium‐diethylenetriaminepentaacetic acid were derived from the reference AIF values and averaged to obtain a cohort‐averaged AIF. Influx rate constants (K_i) and proton distribution volumes at zero time (V_p + V_o) were estimated with Patlak plots of AIF‐I, hypothetical AIFs, and cohort‐averaged AIFs and tissue ΔR₁ data. For the regions of interest, the K_is estimated with AIF‐I were slightly but not significantly higher than those obtained with hypothetical AIFs and cohort‐averaged AIF. In contrast, V_p + V_o was significantly higher when calculated with AIF‐I. Similar estimates of K_i and V_p + V_o were obtained with hypothetical AIFs and cohort‐averaged AIF. In summary, AIF‐I underestimated the reference AIF; this shortcoming had little effect on the K_i calculated by Patlak plot but produced a significant overestimation of V_p + V_o. Magn Reson Med 63:1502–1509, 2010. © 2010 Wiley‐Liss, Inc.     

BOLD imaging in the mouse brain using a turboCRAZED sequence at high magnetic fields

Functional MRI (fMRI) based on the detection of intermolecular double‐quantum coherences (iDQC) has previously been shown to provide pronounced activation signal. For fMRI in small animals at very high magnetic fields, the essential fast gradient echo‐based readout methods become problematic. Here, rapid intermolecular double‐quantum coherence (iDQC) imaging was implemented, combining the iDQC preparation sequence with a Turbo spin echo‐like readout. Four‐step phase cycling and a novel intensity‐ordered k‐space encoding scheme with separate acquisition of odd and even echoes were essential to optimize signal to noise ratio efficiency. Compared with a single echo readout of iDQC signal, acceleration of factor 16 was achieved in phantoms using the novel method at 17.6 Tesla. In vivo, echo trains consisting of 32 echoes were possible and images of the mouse brain were obtained in 30 s. The blood oxygen level dependent (BOLD) effect in the mouse brain upon change of breathing gas was observed as average signal change of (6.3 ± 1.1)% in iDQC images. Signal changes in conventional multi spin echo images were (4.4 ± 2.3)% and (8.3 ± 3.8)% with gradient echo methods. Combination of T₂*‐weighting with the fast iDQC sequence may yield higher signal changes than with either method alone, and establish fast iDQC imaging a robust tool for high field fMRI in small animals. Magn Reson Med 60:850–859, 2008. © 2008 Wiley‐Liss, Inc.