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.     

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.     

Longitudinal in vivo susceptibility contrast MRI measurements of LS174T colorectal liver metastasis in nude mice

Purpose

To characterize longitudinal tumor progression in a murine orthotopic model of liver metastasis using susceptibility contrast magnetic resonance imaging (MRI).

Materials and Methods

Nude mice were inoculated intrasplenically with LS174T colorectal carcinoma cells 24 hours postadministration of 2.5 mgFe/kg of the ultrasmall superparamagnetic iron oxide particle preparation feruglose. Contiguous T₂ and T₂*‐weighted multislice MR images were acquired 10, 15, 20, 25, 30, and 35 days postinoculation to longitudinally evaluate metastatic progression. Functional tumor vasculature and hypoxia were histologically evaluated at the final timepoint using Hoechst 33342 uptake, pimonidazole and hematoxylin and eosin staining. A parallel cohort of subcutaneous tumors was included for comparison.

Results

All intrasplenically inoculated mice developed liver metastases, evident in both T₂*‐ and T₂‐weighted images as high‐signal deposits, compared to feruglose‐nulled normal liver. Small lesions were detected as early as day 10 and all mice exhibited progressing lesions over 35 days. Liver metastases took longer to establish, but exhibited a similar volume doubling time to the subcutaneously propagated tumors of ≈2–3 days. Different functional tumor vascular architectures between the two growth sites were apparent.

Conclusion

Susceptibility‐contrast MRI using a single dose of feruglose can be used to easily detect and longitudinally monitor orthotopically propagated liver metastases in vivo. J. Magn. Reson. Imaging 2008;9999:1451–1458. © 2008 Wiley‐Liss, Inc.     

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.     

Quantification of the magnetic resonance signal response to dynamic (C)O2‐enhanced imaging in the brain at 3 T: R*2 BOLD vs. balanced SSFP

Purpose:

To compare two magnetic resonance (MR) contrast mechanisms, R*₂ BOLD and balanced SSFP, for the dynamic monitoring of the cerebral response to (C)O₂ respiratory challenges.

Materials and Methods:

Carbogen and CO₂‐enriched air were delivered to 9 healthy volunteers and 1 glioblastoma patient. The cerebral response was recorded by two‐dimensional (2D) dynamic multi‐gradient‐echo and passband‐balanced steady‐state free precession (bSSFP) sequences, and local changes of R*₂ and signal intensity were investigated. Detection sensitivity was analyzed by statistical tests. An exponential signal model was fitted to the global response function delivered by each sequence, enabling quantitative comparison of the amplitude and temporal behavior.

Results:

The bSSFP signal changes during carbogen and CO₂/air inhalation were lower compared with R*₂ BOLD (ca. 5% as opposed to 8–13%). The blood‐oxygen‐level‐dependent (BOLD) response amplitude enabled differentiation between carbogen and CO₂/air by a factor of 1.4–1.6, in contrast to bSSFP, where differentiation was not possible. Furthermore, motion robustness and detection sensitivity were higher for R*₂ BOLD.

Conclusion:

Both contrast mechanisms are well suited to dynamic (C)O₂‐enhanced MR imaging, although the R*₂ BOLD mechanism was demonstrated to be superior in several respects for the chosen application. This study suggests that the R*₂ BOLD and bSSFP‐response characteristics are related to different physiologic mechanisms. J. Magn. Reson. Imaging 2010;31:1300–1310. © 2010 Wiley‐Liss, Inc.     

Distribution of cardiac iron measured by magnetic resonance imaging (MRI)-R*2

Purpose

To assess regional iron distribution by magnetic resonance imaging (MRI)‐R₂* within the heart of patients with β‐thalassemia major (TM) and other iron overload diseases.

Materials and Methods

Breathhold electrocardiogram (ECG)‐gated MRI (1.5 T) of the heart was used for the measurement of transverse relaxation rates R₂* in 32 patients (11–79 years). In a mid‐papillary short‐axis slice divided into septal, anterior, lateral, and posterior quadrants, R₂* was analyzed from region of interest (ROI)‐based signal intensities from 12 echo times (TE = 1.3–26 msec). Typical boundary effects were evaluated in detail.

Results

The segmentation of the cardiac wall resulted in highly significant correlations of R₂* between septal and all other quadrants. In the patient group with R₂* < 50 s^?1 (normal), all quadrants show higher normalized median rates (126%–174%) than the septum (P < 10^?4), while this was relatively smaller in the group with septal R₂* > 50 s^?1. Typical boundary effects on segmental R₂* from blood, lung tissue, epicardial fat, and hepatic iron could not be easily separated from segmental iron distribution.

Conclusion

The measurement of MRI‐R2* in the interventricular septum is the least affected method by boundary effects to detect patients with iron overload at risk of developing heart failure. J. Magn. Reson. Imaging 2010;32:1104–1109. © 2010 Wiley‐Liss, Inc.

     

Spectroscopic imaging of the water resonance with short repetition time to study tumor response to hyperoxia

A variety of treatments that modulate tumor oxygen tension are used clinically to improve the outcome of radiotherapy. High resolution, noninvasive measurements of the effects of these treatments would greatly facilitate the development of improved therapies and could guide treatment of cancer patients. Previous work demonstrated that magnetic resonance (MR) gradient echo imaging of the water proton resonance detects changes in T₂* and T₁ in tumors during hyperoxia that may reflect increased tumor oxygenation. This report describes the use of high resolution MR spectroscopic imaging with short repetition time (TR = 0.2 s) to improve the accuracy with which changes in T₂* and T₁ are measured. Mammary adenocarcinomas grown in the hind limbs of rats were studied. Carbogen inhalation was used to induce hyperoxia. A single 2-mm slice through the center of tumors and underlying muscle was imaged at 4.7 Tesla with in-plane resolution of approximately 1.2 mm and frequency resolution of 5.8 Hz. The peak integral increased by an average of 6% in tumors during carbogen inhalation suggesting a decrease in T₁ (n = 8, P <0.001). Peak height increased by an average of 15% in tumors during carbogen inhalation (n = 8, P <0.001). The large difference between increases in peak height and peak integral demonstrates that the width of the water resonance decreased. Assuming a Lorentzian lineshape, an average increase of 12% in T₂* was observed in tumors. In muscle, peak integral and peak height increased slightly (about 1.2% and 3%. respectively; P <0.02) during carbogen inhalation but no significant change in T₂*was observed. Spectroscopic imaging detects changes in the water proton resonance in tumors during hyperoxia accurately and reproducibly with high signal-to-noise ratio and allows clear separation of T₁ and T₂* effects. Increases in T₂* may be due to decreased deoxyhemoglobin in tumor blood vessels (i.e., the BOLD effect) and may provide a clinically useful index of increases in tumor oxygenation.     

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.     

Improved MRI R2* relaxometry of iron‐loaded liver with noise correction

Accurate and reproducible MRI R₂* relaxometry for tissue iron quantification is important in managing transfusion‐dependent patients. MRI data are often acquired using array coils and reconstructed by the root‐sum‐square algorithm, and as such, measured signals follow the noncentral chi distribution. In this study, two noise‐corrected models were proposed for the liver R₂* quantification: fitting the signal to the first moment and fitting the squared signal to the second moment in the presence of the noncentral chi noise. These two models were compared with the widely implemented offset and truncation models on both simulation and in vivo data. The results demonstrated that the “slow decay component” of the liver R₂* was mainly caused by the noise. The offset model considerably overestimated R₂* values by incorrectly adding a constant to account for the slow decay component. The truncation model generally produced accurate R₂* measurements by only fitting the initial data well above the noise level to remove the major source of errors, but underestimated very high R₂* values due to the sequence limit of obtaining very short echo time images. Both the first and second‐moment noise‐corrected models constantly produced accurate and precise R₂* measurements by correctly addressing the noise problem. Magn Reson Med 70:1765–1774, 2013. © 2013 Wiley Periodicals, Inc.     

Targeting of ultrasmall superparamagnetic iron oxide (USPIO) particles to tumor cells in Vivo by using transferrin receptor pathways

Human transferrin was covalently coupled to ultrasmall superparamagnetic iron oxide (USPIO) particles, and the trans-ferrin-USPIO obtained was investigated in vivo in experimental SMT/2A tumor-bearing rats (rat mammary carcinoma). Physicochemical characterization showed an overall size of 36 nm (DLS) with a core size of 5 nm (TEM). Relaxivities were R,₁ = 23.6 and R₂ = 52.1 liter/mmol · s (0.47 T). Bound transferrin was 280 μg/mg of iron. Pharmacokinetic investigations revealed a half-life of 17 min in normal rats. The MR evaluation of tumor signal intensity over time showed a 40% (range 25–55%) signal reduction 150 min after injection with the reduction persisting for at least 8 h. Control experiments using the parent USPIO compound or USPIO labeled with a nonspecific human serum albumin (HSA-USPIO) showed a change of only 10% (range 5–15%) in tumor signal intensity over time. The results demonstrate that a combination of the USPIO relaxivity properties with the specificity of transferrin-medi-ated endocytosis allows in vivo detection of tumors by MR imaging.     

Respiratory self‐gated multiple gradient recalled echo sequence for free‐breathing abdominal R2* mapping

Abdominal effective transverse relaxation rate (R₂*) mapping is critical for a wide range of applications. However, respiratory motion can lead to significant image quality deterioration and R₂* overestimation. For this work, we explored the feasibility of combining respiratory self‐gating techniques with a multiple gradient‐recalled echo sequence for free‐breathing abdominal R₂* measurements. In a series of eight normal volunteers, respiratory self‐gated–multiple gradient‐recalled echo methods effectively avoided motion artifacts to produce quantitative R₂* measurements in liver, spleen, and kidneys that were comparable to R₂* measurements produced while breath‐holding. Respiratory self‐gated–multiple gradient‐recalled echo methods demonstrated the potential to avoid the need for breath‐holding during abdominal R₂* mapping. For clinical application, respiratory self‐gated–multiple gradient‐recalled echo approaches could be particularly useful for R₂* measurements in those patients unable or unwilling to sustain sufficiently long breath‐holds to avoid motion artifacts. Magn Reson Med, 2011. © 2011 Wiley‐Liss, Inc.     

Comparison of 1H blood oxygen level–dependent (BOLD) and 19F MRI to investigate tumor oxygenation

Fluorine‐19 [¹⁹F] MRI oximetry and ¹H blood oxygen level–dependent (BOLD) MRI were used to investigate tumor oxygenation in rat breast 13762NF carcinomas, and correlations between the techniques were examined. A range of tissue oxygen partial pressure (pO₂) values was found in the nine tumors while the anesthetized rats breathed air, with individual tumor pO₂ ranging from a mean of 1 to 36 torr and hypoxic fraction (HF10) (<10 torr) ranging from 0% to 75%, indicating a large intra‐ and intertumor heterogeneity. Breathing oxygen produced significant increase in tumor pO₂ (mean ΔpO₂ = 50 torr) and decrease in HF₁₀ (P < 0.01). ¹H BOLD MRI observed using a spin echo‐planar imaging (EPI) sequence revealed a heterogeneous response and significant increase in mean tumor signal intensity (SI) (ΔSI = 7%, P < 0.01). R measured by multigradient‐echo (MGRE) MRI decreased significantly in response to oxygen (mean ΔR = ?4 s^?1; P < 0.05). A significant correlation was found between changes in mean tumor pO₂ and mean EPI BOLD ΔSI accompanying oxygen breathing (r² > 0.7, P < 0.001). Our results suggest that BOLD MRI provides information about tumor oxygenation and may be useful to predict pO₂ changes accompanying interventions. Significantly, the magnitude of the BOLD response appears to be predictive for residual tumor HFs. Magn Reson Med, 2009. © 2009 Wiley‐Liss, Inc.     

Reproducibility and correlation between quantitative and semiquantitative dynamic and intrinsic susceptibility‐weighted MRI parameters in the benign and malignant human prostate

Purpose:

To assess the reproducibility of relaxivity‐ and susceptibility‐based dynamic contrast‐enhanced magnetic resonance imaging (MRI) in the benign and malignant prostate gland and to correlate the kinetic parameters obtained.

Materials and Methods:

Twenty patients with prostate cancer underwent paired scans before and after androgen deprivation therapy. Quantitative parametric maps for T₁‐ and T₂*‐weighted parameters were calculated (K^trans, k_ep,v_e, IAUC₆₀, rBV, rBF, and R₂*). The reproducibility of and correlation between each parameter were determined using standard methods at both timepoints.

Results:

T₁‐derived parameters are more reproducible than T₂*‐weighted measures, both becoming more variable following androgen deprivation (variance coefficients for prostate K^trans and rBF increased from 13.9%–15.8% and 42.5%–90.8%, respectively). Tumor R₂* reproducibility improved after androgen ablation (23.3%–11.8%). IAUC₆₀ correlated strongly with K^trans, v_e, and k_ep (all P < 0.001). R₂* did not correlate with other parameters.

Conclusion:

This study is the first to document the variability and repeatability of T₁‐ and T₂*‐weighted dynamic MRI and intrinsic susceptibility‐weighted MRI for the various regions of the human prostate gland before and after androgen deprivation. These data provide a valuable source of reference for groups that plan to use dynamic contrast‐enhanced MRI or intrinsic susceptibility‐weighted MRI for the assessment of treatment response in the benign or malignant prostate. J. Magn. Reson. Imaging 2010;32:155–164. © 2010 Wiley‐Liss, 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.     

Optimization of iron oxide nanoparticle detection using ultrashort echo time pulse sequences: Comparison of T1, T2*, and synergistic T1 − T2* contrast mechanisms

Iron oxide nanoparticles (IONPs) are used in various MRI applications as negative contrast agents. A major challenge is to distinguish regions of signal void due to IONPs from those due to low signal tissues or susceptibility artifacts. To overcome this limitation, several positive contrast strategies have been proposed. Relying on IONP T₁ shortening effects to generate positive contrast is a particularly appealing strategy because it should provide additional specificity when associated with the usual negative contrast from effective transverse relaxation time (T₂*) effects. In this article, ultrashort echo time imaging is shown to be a powerful technique which can take full advantage of both contrast mechanisms. Methods of comparing T₁ and T₂* contrast efficiency are described and general rules that allow optimizing IONP detection sensitivity are derived. Contrary to conventional wisdom, optimizing T₁ contrast is often a good strategy for imaging IONPs. Under certain conditions, subtraction of a later echo signal from the ultrashort echo time signal not only improves IONP specificity by providing long T₂* background suppression but also increases detection sensitivity, as it enables a synergistic combination of usually antagonist T₁ and T₂* contrasts. In vitro experiments support our theory, and a molecular imaging application is demonstrated using tumor‐targeted IONPs in vivo. Magn Reson Med, 2011. © 2011 Wiley‐Liss, Inc.     

Investigation of relationships between transverse relaxation rate,diffusion coefficient,and labeled cell concentration in ischemic rat brain using MRI

MRI has been used to evaluate labeled cell migration and distribution. However, quantitative determination of labeled cell concentration using MRI has not been systematically investigated. In the current study, we investigated the relationships between labeled cell concentration and MRI parameters of transverse relaxation rate, R₂, and apparent diffusion coefficient (ADC), in vitro in phantoms and in vivo in rats after stroke. Significant correlations were detected between iron concentration or labeled cell concentration and MRI measurements of R₂, ADC, and ADC×R₂ in vitro. In contrast, in vivo labeled cell concentration did not significantly correlate with R₂, ADC, and ADC×R₂. A major factor for the absence of a significant correlation between labeled cell concentration and MRI measurements in vivo may be attributed to background effects of ischemic tissue. By correcting the background effects caused by ischemic damage, ΔR₂ (difference in R₂ values in the ischemic tissue with and without labeled cells) exhibited a significant correlation to labeled cell concentration. Our study suggests that MRI parameters have the potential to quantitatively determine labeled cell concentration in vivo. Magn Reson Med, 2009. © 2008 Wiley‐Liss, Inc.     

Estimation of liver T*2 in transfusion‐related iron overload in patients with weighted least squares T*2 IDEAL

MRI imaging of hepatic iron overload can be achieved by estimating T₂* values using multiple‐echo sequences. The purpose of this work is to develop and clinically evaluate a weighted least squares algorithm based on T₂* Iterative Decomposition of water and fat with Echo Asymmetry and Least‐squares estimation (IDEAL) technique for volumetric estimation of hepatic T₂* in the setting of iron overload. The weighted least squares T₂* IDEAL technique improves T₂* estimation by automatically decreasing the impact of later, noise‐dominated echoes. The technique was evaluated in 37 patients with iron overload. Each patient underwent (i) a standard 2D multiple‐echo gradient echo sequence for T₂* assessment with nonlinear exponential fitting, and (ii) a 3D T₂* IDEAL technique, with and without a weighted least squares fit. Regression and Bland–Altman analysis demonstrated strong correlation between conventional 2D and T₂* IDEAL estimation. In cases of severe iron overload, T₂* IDEAL without weighted least squares reconstruction resulted in a relative overestimation of T₂* compared with weighted least squares. Magn Reson Med, 2011. © 2011 Wiley‐Liss, Inc.     

Temporal dependence of in vivo USPIO-enhanced MRI signal changes in human carotid atheromatous plaques

Introduction  Ultrasmall superparamagnetic iron oxide (USPIO)-enhanced MRI has been shown to be a useful modality to image activated macrophages in vivo, which are principally responsible for plaque inflammation. This study determined the optimum imaging time-window to detect maximal signal change post-USPIO infusion using T₁-weighted (T₁w), T₂*-weighted (T₂*w) and quantitative T₂* (qT₂*) imaging. Methods  Six patients with an asymptomatic carotid stenosis underwent high resolution T₁w, T₂*w and qT₂* MR imaging of their carotid arteries at 1.5 T. Imaging was performed before and at 24, 36, 48, 72 and 96 h after USPIO (Sinerem™, Guerbet, France) infusion. Each slice showing atherosclerotic plaque was manually segmented into quadrants and signal changes in each quadrant were fitted to an exponential power function to model the optimum time for post-infusion imaging. Results  The power function determining the mean time to convergence for all patients was 46, 41 and 39 h for the T₁w, T₂*w and qT₂* sequences, respectively. When modelling each patient individually, 90% of the maximum signal intensity change was observed at 36 h for three, four and six patients on T₁w, T₂*w and qT₂*, respectively. The rates of signal change decrease after this period but signal change was still evident up to 96 h. Conclusion  This study showed that a suitable imaging window for T₁w, T₂*w and qT₂* signal changes post-USPIO infusion was between 36 and 48 h. Logistically, this would be convenient in bringing patients back for one post-contrast MRI, but validation is required in a larger cohort of patients. Sources of funding: GlaxoSmithKline and The Stroke Association     

BOLD MRI monitoring of changes in cerebral perfusion induced by acetazolamide and hypercarbia in the rat

To evaluate MRI methods for estimating cerebrovascular reserve, we computed changes in the R₂* and R₂, transverse relaxation rate and apparent diffusion coefficient (ADC) at 2.0 Tesla in five rats after administration of 30 mg of acetazolamide and in four rats during inhalation of 20% carbon dioxide gas. Significant decreases in R₂*, corresponding to increases in gradient echo MRI signals, occurred in both the acetazolamide (average change ?8.3%, P = 0.005) and the carbon dioxide (?2.7%, P = 0.009) treated animals. The computed values for R₂ and ADC were unchanged. The magnitude of the gradient echo MRI changes observed should permit anatomic mapping of blood flow reactivity patterns in normal human subjects and in patients at risk for cerebrovascular disease.     

T2*‐relaxivity contrast imaging: First results

In this study, T₂*‐ relaxivity contrast imaging (RCI) is proposed for new contrast generation in MRI. The method produces images of relaxivities r*_2,vasc and r*_2,EES caused by susceptibility gradients across the vessel walls and cell membranes, respectively. The sensitivity to noise was assessed with a simulation study, and initial results are presented for five colorectal tumor xenografts in nude mice. Simulations show that the new relaxivity parameters are at least as accurate and precise as standard parameters such as plasma volume and interstitial volume. Mean values of both relaxivities were significantly different (r*_2,vasc = 10.9 ± 2.9 mM^?1 s^?1 and r*_2,EES = 15.6 ± 2.6 mM^?1 s^?1). r*_2,vasc (r = 0.67) and r*_2,EES (r = 0.52) were weakly correlated with plasma volume and interstitial volume, respectively. Images of r*_2,vasc and r*_2,EES reveal a different tumor structure than plasma volume and interstitial volume maps. These results suggest that relaxivity contrast imaging is practically feasible and might offer supplementary information compared to dynamic contrast‐enhanced‐MRI. Magn Reson Med, 2013. © 2012 Wiley Periodicals, Inc.