BOLD MRI response to hypercapnic hyperoxia in patients with meningiomas: correlation with Gadolinium-DTPA uptake rate

Because meningiomas tend to recur after (partial) surgical resection, radiotherapy is increasingly being applied for the treatment of these tumors. Radiation dose levels are limited, however, to avoid radiation damage to the surrounding normal tissue. The radiosensitivity of tumors can be improved by increasing tumor oxygen levels. The aim of this study was to investigate if breathing a hyperoxic hypercapnic gas mixture could improve the oxygenation of meningiomas. Blood oxygen level-dependent magnetic resonance imaging and dynamic Gadolinium (Gd)-DTPA contrast-enhanced MRI were used to assess changes in tumor blood oxygenation and vascularity, respectively. Ten meningioma patients were each studied twice; without and with breathing a gas mixture consisting of 2% CO(2) and 98% O(2). Values of T(2)* and the Gd-DTPA uptake rate k(ep) were calculated under both conditions. In six tumors a significant increase in the value of T(2)* in the tumor was found, suggesting an improved tumor blood oxygenation, which exceeded the effect in normal brain tissue. Contrarily, two tumors showed a significant T(2)* decrease. The change in T(2)* was found to correlate with both k(ep) and with the change in k(ep). The presence of both vascular effects and oxygenation effects and the heterogeneous response to hypercapnic hyperoxia necessitates individual assessment of the effects of breathing a hyperoxic hypercapnic gas mixture on meningiomas. Thus, the current MRI protocol may assist in radiation treatment selection for patients with meningiomas.     

Flow and oxygenation dependent (FLOOD) contrast MR imaging to monitor the response of rat tumors to carbogen breathing

Gradient recalled echo (GRE) images are sensitive to both paramagnetic deoxyhaemoglobin concentration (via T2*) and flow (via T1*). Large GRE signal intensity increases have been observed in subcutaneous tumors during carbogen (5% carbon dioxide, 95% oxygen) breathing. We term this combined effect flow and oxygenation-dependent (FLOOD) contrast. We have now used both spin echo (SE) and GRE images to evaluate how changes in relaxation times and flow contribute to image intensity contrast changes. T1-weighted images, with and without outer slice suppression, and calculated T2, T2* and "flow" maps, were obtained for subcutaneous GH3 prolactinomas in rats during air and carbogen breathing. T1-weighted images showed bright features that increased in size, intensity and number with carbogen breathing. H&E stained histological sections confirmed them to be large blood vessels. Apparent T1 and T2 images were fairly homogeneous with average relaxation times of 850 ms and 37 ms, respectively, during air breathing, with increases of 2% for T1 and 11% for T2 during carbogen breathing. The apparent T2* over all tumors was very heterogeneous, with values between 9 and 23 ms and localized increases of up to 75% during carbogen breathing. Synthesised "flow" maps also showed heterogeneity, and regions of maximum increase in flow did not always coincide with maximum increases in T2*. Carbogen breathing caused a threefold increase in arterial rat blood PaO2, and typically a 50% increase in tumor blood volume as measured by 51Cr-labelled RBC uptake. The T2* increase is therefore due to a decrease in blood deoxyhaemoglobin concentration with the magnitude of the FLOOD response being determined by the vascular density and responsiveness to blood flow modifiers. FLOOD contrast may therefore be of value in assessing the magnitude and heterogeneity of response of individual tumors to blood flow modifiers for both chemotherapy, antiangiogenesis therapy in particular, and radiotherapy.     

Direct measurement of oxygen extraction with fMRI using 6% CO2 inhalation

The blood-oxygenation-level-dependent (BOLD) signal is an indirect hemodynamic signal that is sensitive to cerebral blood flow (CBF), cerebral blood volume (CBV) and cerebral metabolic rate of oxygen. Therefore, the BOLD signal amplitude and dynamics cannot be interpreted unambiguously without additional physiological measurements, and thus, there remains a need for a functional magnetic resonance imaging (fMRI) signal, which is more closely related to the underlying neuronal activity. In this study, we measured CBF with continuous arterial spin labeling, CBV with an exogenous contrast agent and BOLD combined with intracortical electrophysiological recording in the primary visual cortex of the anesthetized monkey. During inhalation of 6% CO2, it was observed that CBF and CBV are not further increased by a visual stimulus, although baseline CBF for 6% CO2 is below the maximal value of CBF. In contrast, the electrophysiological response to the stimulation was found to be preserved during hypercapnia. As a consequence, the simultaneously measured BOLD signal responds negatively to a visual stimulation for 6% CO2 inhalation in the same voxels responding positively during normocapnia. These observations suggest that the fMRI response to a sensory stimulus for 6% CO2 inhalation occurs in the absence of a hemodynamic response, and it therefore directly reflects oxygen extraction into the tissue.     

Gas challenge-blood oxygen level-dependent (GC-BOLD) MRI in the rat Novikoff hepatoma model

Purpose

The purpose of the study was to investigate the relationship between gas challenge-blood oxygen level-dependent (GC-BOLD) response angiogenesis and tumor size in rat Novikoff hepatoma model.

Materials and Methods

Twenty adult male Sprague-Dawley rats (weighting 301-325 g) were used for our Animal Care and Use Committee-approved experiments. N1-S1 Novikoff hepatomas were grown in 14 rats with sizes ranging from 0.42 to 2.81 cm. All experiments were performed at 3.0 T using a custom-built rodent receiver coil. A multiple gradient-echo sequence was used for R2^? measurements, first during room air (78% N₂/20% O₂) breathing and then after 10 min of carbogen (95% O₂/5% CO₂) breathing. After image acquisition, rats were euthanized, and the tumors were harvested for histological evaluation.

Results

The R2^? change between air and carbogen breathing for small hepatomas was positive; R2^? changes changed to negative values for larger hepatomas. We found a significant positive correlation between tumor R2^? change and tumor microvessel density (MVD) (r=0.798, P=.001) and a significant inverse correlation between tumor R2^? change and tumor size (r=−0.840, P<.0001).

Conclusions

GC-BOLD magnetic resonance imaging measurements are well correlated to MVD levels and tumor size in the N1-S1 Novikoff hepatoma model; GC-BOLD measurements may serve as noninvasive biomarkers for evaluating angiogenesis and disease progression and/or therapy response.     

The measurement of fetal liver T(*)(2) in utero before and after maternal oxygen breathing: progress towards a non-invasive measurement of fetal oxygenation and placental function

Utero-placental insufficiency is thought to be a major cause of growth retardation in utero and an important risk factor in the perinatal period. The purpose of this study was to investigate whether MRI could detect changes of fetal oxygenation, based on the blood oxygenation level dependence (BOLD) of the MRI tissue signal. Nine third trimester women (34-38 weeks) with normal pregnancies underwent abdominal MRI examinations. Following localization of the fetal liver using T(2)-weighted single-shot HASTE scans, up to 7 breath-held transaxial single-slice gradient-echo image sets were obtained through the fetal liver. The mother then commenced oxygen breathing with the imaging procedure repeated after 20 minutes of O(2) breathing. For each image set, T(*)(2) values are calculated using linear regression of log (signal) versus TE for a region of interest within the fetal liver selected by the attending radiologist. Fetal liver T(*)(2) values were calculated before and after O(2) breathing for each multi-echo image acquisition set. A signed rank test was used to test for a significant change in fetal liver T(*)(2) between the pre-O(2) and post-O(2) image sets. A significant increase in T*(2) (alpha < 0.05) was seen in 5 of the 9 fetal livers, a smaller increase (of borderline statistical significance, alpha = 0.057) in 2 livers, and no significant change (alpha > 0.05) in 2 livers. Our study indicates that T(*)(2) measurement of the fetal liver may detect alteration in fetal oxygen level following maternal oxygenation using the BOLD effect. This technique may potentially be applied to the identification and understanding of placental dysfunction in intra-uterine growth retardation.     

Effects of cocaine on blood flow and oxygen metabolism in the rat brain: implications for phMRI

The effects of cocaine on cerebral blood flow and tissue oxygen levels in the rat brain were investigated with concurrent laser Doppler flowmetry and fluorescence quenching spectroscopy. Responses elicited by mild hypercapnia were used as calibration to assess the effects of cocaine on oxidative metabolism. Intravenous cocaine challenge of 0.5 mg/kg induced significant increases in tissular oxygenation and perfusion in all regions investigated (primary motor cortex, medial prefrontal cortex and dorsal striatum). Mild hypercapnia, a challenge that affects haemodynamics but not metabolism, elicited comparable changes in blood flow but substantially larger changes in tissue oxygen levels. These differences in tissue oxygen build-up suggest that increased oxidative metabolism is a significant component of the cerebral metabolic response to acute cocaine challenge. The implications for the interpretation of pharmacological MRI data are discussed.     

Amide proton relaxation measurements employing a highly deuterated protein

Proton NMR longitudinal and transverse relaxation rates of unlabelled proteins are generally dominated by the many 1H-1H dipolar interactions so that spin diffusion, rather than molecular or internal motions, governs longitudinal relaxation. Here, relaxation measurements of backbone amide proton (1H(N)) magnetisations have been carried out employing the 99% 2H, 98% 15N labelled, small 2F2 protein domain in 10%/90% H(2)O/D(2)O solution. Under these conditions, the longitudinal relaxation rates exhibit time constants, T(1)*=1/R(1)* if described by a mono-exponential, within the range of 3.0 to 18.7s-a wide range which indicates that the phenomenon of spin diffusion has been greatly reduced. The majority of 1H(N) nuclei in this sample (pH 4.0 and 5 degrees C) exhibit chemical exchange with solvent that couples their longitudinal relaxation to that of the solvent. For the subset of 1H(N) nuclei not undergoing detectable solvent chemical exchange, the R(1)* rates correlate well with their individual 1H(N,O)/2H(N,O) structural environments. The correlation for corresponding transverse relaxation rates, R(2)* was found to be less good. Longitudinal relaxation measurements in 1%/99% H(2)O/D(2)O solution identify a further subset of 1H(N) nuclei which exhibit essentially indistinguishable R(1)* rates in both 1% and 10% H(2)O, implying that averaging of rates from spin diffusion processes and different 2F2 isotopomer populations are negligible for these 1H(N) sites. In addition to a high sensitivity to structural parameters, model calculations predict 1H(N) relaxation rates to exhibit pronounced sensitivity to internal dynamics.     

Oxygen-sensitive 19F NMR imaging of the vascular system in vivo

The fluorine nuclear magnetic resonance spin-lattice relaxation rate (1/T1) of the perfluorochemical blood substitute perfluorotripropylamine (FTPA) is very sensitive to oxygen tension. This presents the possibility of measuring blood oxygen tension by 19F MR imaging. We obtained oxygen-sensitive 19F NMR images of the circulatory system of rats infused with emulsified FTPA. Blood oxygenation was assessed under conditions of both air- and 100% O2-breathing. T1 relaxation times were derived from MR images using a partial saturation pulse sequence. The T1 times were compared with a phantom calibration curve to calculate average blood pO2 values in the lung, liver, and spleen. The results showed marked, organ-specific increases in blood oxygen tension when the rat breathed 100% O2 instead of air.     

Increasing mean airway pressure reduces functional MRI (fMRI) signal in the primary visual cortex

Changes in both blood flow and blood oxygenation determine the functional MRI (fMRI) signal. In the present study factors responsible for blood oxygenation (e.g., FiO(2)) were held constant so that changes in pixel count would above all reflect changes in regional cerebral blood flow (rCBF). Continuous positive airway pressure (CPAP) breathing at 12 cm H(2)O, which was previously shown to influence rCBF, was applied in human volunteers (n = 19) to investigate the sensitivity of fMRI for changes in rCBF caused by increased mean airway pressure. Increasing the mean airway pressure decreased the pixel count in the primary visual cortex (median (range)): baseline: 219 (58-425) pixels vs. CPAP (12 cm H(2)O): 92 (0-262) pixels). These findings indicate that fMRI is sensitive to detect a reduced rCBF-response in the primary visual cortex. The underlying mechanism is likely to be a reduced basal rCBF due to constriction and/or compression of postcapillary venoles during CPAP breathing. These findings are important for interpreting fMRI results in awake and in artificially respirated patients, in whom positive airway pressure is used to improve pulmonary function during the diagnostic procedure.     

Hemodynamic scaling of fMRI-BOLD signal: validation of low-frequency spectral amplitude as a scalability factor

Functional magnetic resonance imaging blood-oxygenation-level-dependent (fMRI-BOLD) signal representing neural activity may be optimized by discriminating MR signal components related to neural activity and those related to intrinsic properties of the cortical vasculature. The objective of this study was to reduce the hemodynamic change independent of neural activity to obtain a scaled fMRI-BOLD response using two factors, namely, low-frequency spectral amplitude (LFSA) and breath-hold amplitude (BHA). Ten subjects (age range, 22–38 years) were scanned during four task conditions: (a) rest while breathing room air, (b) bilateral finger tapping while breathing room air, (c) rest during a partial inspirational breath-hold, and (d) rest during moderate hypercapnia (breathing 5% CO₂, 20% O₂ and 75% N₂). In all subjects who breathed 5% CO₂, regions with significant BOLD response during breath-hold correlated significantly with the percent signal increase during 5% CO₂ inhalation. Finger-tapping-induced responses in the motor cortex were diminished to a similar extent after scaling using either LFSA or BHA. Inter- and intrasubject variation in the amplitude of the BOLD signal response reduced after hemodynamic scaling using LFSA or BHA. The results validated the hemodynamic amplitude scaling using LFSA with the earlier established BHA. LFSA free from motor-task contamination can be used to calibrate the fMRI-BOLD response in lieu of BHA or hypercapnia to minimize intra- and intersubject variation arising from vascular anatomy and vasodilative capacity.     

The lag of cerebral hemodynamics with rapidly alternating periodic stimulation: modeling for functional MRI

A mathematical model that characterizes the response of venous oxygenation to changes in cerebral blood flow (rCBF) and oxygen consumption has been previously presented. We use this model to examine the dampening phenomenon in functional MRI (fMRI) signals with rapidly alternating periodic stimulation bursts. Using a mass balance approach, the equations for an input-output model are derived and solved using Matlab (the Math Works Inc.). Changes in venous oxygenation are related to the results of fMRI experiments using progressively shorter periods of stimulation. An impulse-response function for the model is derived in an attempt to explore the source of the lag in cerebral hemodynamics. Increasing the frequency of stimulation bursts eventually produces a dampening in the fMRI signal. The dampening phenomenon in fMRI signals occurs with stimulation of high frequency on-off alternation. The dynamics of signal dampening, as well as the impulse-response function of a blood oxygen level-dependent model, lend strong indirect support to the hypothesis that blood oxygen level-dependent contrast at the level of the venous blood pool, rather than R1 inflow effects or changes in oxygenation at the level of the capillary bed, underlies the observed signal changes in fMRI.     

In vitro labeling and MRI of mesenchymal stem cells from human umbilical cord blood

OBJECTIVE: The aim of this study was to label human umbilical cord blood mesenchymal stem cells (MSCs) with poly-l-lysine (PLL)-conjugated superparamagnetic iron oxide particles and to obtain magnetic resonance (MR) images of the labeled MSCs' suspension at 1.5 T. MATERIAL AND METHODS: PLL was conjugated with iron oxide to form superparamagnetic particles called Fe(2)O(3)-PLL. Human umbilical cord blood MSCs were isolated, purified, expanded and incubated with Fe(2)O(3)-PLL. Prussian blue stain was performed to show intracellular iron; spectrometry was used to quantify iron uptake within cells. Tetrazolium salt (MTT) assay was applied to evaluate toxicity and proliferation of MSCs labeled with various concentrations of Fe(2)O(3)-PLL. The cell apoptosis rate was determined by annexin V/propichium iodide (PI) double staining method. Vials containing cells underwent MR imaging (MRI) with T(1), T(2) and T(2)* weighted MRI. RESULTS: Iron-containing intracytoplasmatic vesicles could be observed clearly with Prussian blue staining in all samples except the unlabeled control. The iron content per cell determined by spectrometry was 64.51+/-10.32 pg. Among MSCs with and without labeling of various concentrations of Fe(2)O(3)-PLL, MTT values of light absorption had no statistically significant difference (Kruskal-Wallis test, chi(2)=10.35, P=.17). A concentration at 20 mug/ml of iron appeared most suitable for incubating cells. Of labeled and unlabeled MSCs, the early [annexin V-fluorescein isothiocyanate (FITC)-positive/PI-negative] and late (annexin V-FITC-positive/PI-positive) apoptotic cells were 10.34+/-0.43%/11.36+/-1.30% and 4.01+/-1.76%/2.98+/-1.37%, respectively, and there were no significant differences between them (P>.05). T(2) weighted image (WI) and T(2)*WI demonstrated significant decrease of signal intensity (SI) in vials containing 1 x 10(6) (1 day), 1x10(6) (8 days) and 5 x 10(5) labeled cells, in comparison with unlabeled cells (P<.05). The percentage change of SI (DeltaSI) was significantly higher in 10(6) labeled cells after 1-day culture than that in the same number of labeled cells after 8-day culture and that in 5 x 10(5) labeled cells, particularly on T(2)*WI (P<.05). Among pulse sequences, T(2)*WI demonstrated the highest DeltaSI (P<.05). CONCLUSION: The human umbilical cord blood MSCs can be labeled with Fe(2)O(3)-PLL without significant change in viability and apoptosis. The suspension of labeled MSCs can be imaged with standard 1.5-T MR equipment.     

H3O+, NO+和O+·2离子同九种烷氧基醇化合物反应的研究

在用选择离子流动管质谱(SIFT-MS)分析常用指甲油清洗垫发现大量4-丁酸内脂(γ-butyrolactone, GBL)和2-丁氧基乙醇(2-butoxy-1-ethanol)等挥发性气体后, 运用选择离子流动管(SIFT)对H3O , NO 和O ·2离子同九种烷氧基醇化合物(R1-O-R2OH)之间的反应进行了研究. 获得了这些反应在潮湿空气条件下进行的情况, 并运用产物离子水合物的种类和分布来确认产物离子的结构和反应机理. 还研究了在不同载气压力下进行的反应. 结果表明, 这些化合物同H3O 和NO 的反应都是先生成初生态离子-分子络合物, (H3O .M)*和(NO .M)*, 然后经不同反应渠道生成各种离子产物. 这些初生态络合物同反应体系中存在的气体分子(如氦气, 氮气和氧气分子)的碰撞对最终离子产物的形成和分布也有影响. 这些化合物同O2 ·反应会生成各种离解碎片离子, 但不能确定这些离子是否经由初生态络合物(O2 ·.M)*生成. 该项研究提供了用SIFT-MS在空气和潮湿气体中分析这些化合物所需的反应速率常数和离子产物等动力学数据, 并将进一步应用到药物成瘾及滥用和呼吸道疾病的诊断和分析等领域.     

Feasibility study of myocardial perfusion and oxygenation by noncontrast MRI: comparison with PET study in a canine model

The purpose of this study was to examine the feasibility of quantifying myocardial blood flow (MBF) and rate of myocardial oxygen consumption (MVO(2)) during pharmacologically induced stress without using a contrast agent. The former was measured by the arterial spin labeling (ASL) method and the latter was obtained by measuring the oxygen extraction fraction (OEF) with the magnetic resonance imaging (MRI) blood oxygenation level-dependent effect and Fick's law. The MRI results were compared with the established positron emission tomography (PET) methods. Six mongrel dogs with induced acute moderate left coronary artery stenosis were scanned using a clinical PET and a 1.5-T MRI system, in the same day. Regional MBF, myocardial OEF and MVO(2) were measured with both imaging modalities. Correlation coefficients (R(2)) of the three myocardial indexes (MBF, OEF and MVO(2)) between MRI and PET methods ranged from 0.70 to 0.93. Bland-Altman statistics demonstrated that the estimated precision of the limits of agreement between MRI and PET measurements varied from 18% (OEF) to 37% (MBF) and 45% (MVO(2)). The detected changes in these indexes, at rest and during dobutamine stress, were similar between two image modalities. The proposed noncontrast MRI technique is a promising method to quantitatively assess myocardial perfusion and oxygenation.     

Simultaneous acquisition of perfusion and permeability from corrected relaxation rates with dynamic susceptibility contrast dual gradient echo

This study compared two methods, corrected (separation of T(1) and T(2)* effects) and uncorrected, in order to determine the suitability of the perfusion and permeability measures through Delta R(2)* and Delta R(1) analyses. A dynamic susceptibility contrast dual gradient echo (DSC-DGE) was used to image the fixed phantoms and flow phantoms (Sephadex perfusion phantoms and dialyzer phantom for the permeability measurements). The results confirmed that the corrected relaxation rate was linearly proportional to gadolinium-diethyltriamine pentaacetic acid (Gd-DTPA) concentration, whereas the uncorrected relaxation rate did not in the fixed phantom and simulation experiments. For the perfusion measurements, it was found that the correction process was necessary not only for the Delta R(1) time curve but also for the Delta R(2)* time curve analyses. Perfusion could not be measured without correcting the Delta R(2)* time curve. The water volume, which was expressed as the perfusion amount, was found to be closer to the theoretical value when using the corrected Delta R(1) curve in the calculations. However, this may occur in the low concentration of Gd-DTPA in tissue used in this study. For the permeability measurements based on the two-compartment model, the permeability factor (k(ev); e = extravascular, v = vascular) from the outside to the inside of the hollow fibers was greater in the corrected Delta R(1) method than in the uncorrected Delta R(1) method. The differences between the corrected and the uncorrected Delta R(1) values were confirmed by the simulation experiments. In conclusion, this study proposes that the correction for the relaxation rates, Delta R(2)* and Delta R(1), is indispensable in making accurate perfusion and permeability measurements, and that DSC-DGE is a useful method for obtaining information on perfusion and permeability, simultaneously.     

近红外空间分辨光谱技术及其对新生猪脑缺氧缺血的检测

近红外光谱(NIRS)技术作为一种无创的组织氧检测手段,近年来在脑缺氧缺血的检测方面日益受到重视。文章介绍了自行研制的NIRS仪器(TSAH-100近红外组织血氧无损监测仪)的基本原理及用于新生猪脑氧检测时如何实现传感器与待测脑组织的最佳耦合。检测了28例新生猪在不同氧合状态下的脑组织氧饱和度(regional cerebral oxygen saturation, rSO₂),在缺氧结束后进行了有创的动脉氧饱和度及生理参数的检测。结果表明,NIRS无创测得的脑rSO₂与血气分析有创测得的动脉血氧饱和度(SaO₂)有很好的相关性(p<0.001),并且脑rSO₂与缺氧程度及缺氧后生理参数的变化一致。因此NIRS无创测得的脑rSO₂能直接判断脑氧合状态,可在一定情况下替代有创血气分析,帮助临床无创、简便地诊断脑缺氧缺血。     

A simple non-invasive method to detect and monitor hypercapnia: the sodium [13C]bicarbonate breath test

Arterial partial pressure of carbon dioxide (paCO(2)) is commonly evaluated by an invasive test, the arterial blood gas analysis (ABG). The sodium [(13)C]bicarbonate breath test (SBT) can potentially estimate arterial paCO(2). We studied 55 subjects with respiratory disorders and performed the ABG and the SBT to determine if the SBT can predict hypercapnia. The percentage of (13)CO(2) recovered in exhaled breath at 30 minutes (PDR(30)) alone was able to discriminate clinically significant hypercapnia (>53 mmHg) with a sensitivity of 82 % and specificity of 93 % (p<0.001). To evaluate the clinical utility of the SBT as a non-invasive substitute to repeated ABG, we monitored the progress of seven chronic obstructive pulmonary disease (COPD) patients on therapy with both the ABG and the SBT. The PDR(30) values from the SBT were able to correctly predict improvement or worsening of paCO(2) with 100 % accuracy. In conclusion, the SBT is a simple test that can be used in clinical practice to detect clinically significant hypercapnia and monitor COPD patients before and after therapy.     

Simultaneous measurement of perfusion and oxygenation changes using a multiple gradient-echo sequence: application to human muscle study

We have developed a magnetic resonance imaging (MRI) technique based on a multiple gradient-echo sequence designed to probe perfusion and oxygenation simultaneously within skeletal muscle. Processing of the images acquired at successive echo times (TEs) generates two functional maps: one of the signal intensity (SI) extrapolated to zero echo time, which is sensitive to perfusion; and a second one of R21, which reflects oxygenation. An advantage of the processing procedure lies in the selection of tissue of interest through the profile of T₂1 decay, leading to automatic rejection of pixels containing small vessels. This allows a more specific assessment of tissue perfusion and oxygenation. This technique was demonstrated successfully during post-ischemic reactive hyperemia in human calf. A perfusion peak of 123 mL ×100 g⁻¹ × min⁻¹ was measured immediately after ischemia, whereas R21 value showed an 11.5% decrease at the same time, essentially reflecting blood oxygenation changes. Differences in the time courses of reperfusion and re-oxygenation were observed, oxygenation presenting a slower recovery. The mechanisms responsible for such a differential dynamic response are discussed.     

High-speed spectroscopic imaging for cancellous bone marrow R(2)* mapping and lipid quantification

In this work an interleaved multiple-gradient-echo chemical shift imaging (IMGE-CSI) technique was designed, implemented and evaluated at 1.5 and 4T for high-resolution lipid quantification and R(2)* measurement in-vivo. The method is analogous to echo planar CSI but utilizes conventional gradient echoes, exploiting the principle of spectroscopic bandwidth extension by interleaving temporally offset gradient-echo trains. It is shown that IMGE-CSI is able to measure true fat volume fraction in oil/water mixtures with high accuracy, not possible with Dixon-type methods which approximate the spectrum as consisting of only two spectral components. Correlation of the CSI- derived volume fractions with volumetry afforded r(2) > 0.99 with a slope of 0.98. The method is shown to be able to quantify regional variations in bone marrow composition in vivo with a spatial resolution of 2.5 x 2.5 x 5 mm(3.) R(2)* was obtained by multi-line spectral curve fitting. For the measurement of R(2)* in cancellous bone marrow the method is shown to agree well with time-domain fitting techniques but is superior in instances where the marrow has both hematopoietic and fatty constituents. Finally, excellent inter-scan reproducibility (1% coefficient of variation for global means and medians) was achieved, yielding r(2) = 0.98 of the test-retest correlation for three scans in four test subjects. In conclusion, IMGE-CSI is found to enable highly accurate lipid quantification and measurement of cancellous bone marrow R(2)* at spatial resolutions and scan times typical of standard clinical protocols.     

Assessment of cerebrovascular reactivity with functional magnetic resonance imaging: comparison of CO(2) and breath holding

Cerebral blood flow (CBF) and oxygenation changes following both a simple breath holding test (BHT) and a CO(2) challenge can be detected with functional magnetic resonance imaging techniques. The BHT has the advantage of not requiring a source of CO(2) and acetazolamide and therefore it can easily be performed during a routine MR examination. In this study we compared global hemodynamic changes induced by breath holding and CO(2) inhalation with blood oxygenation level dependent (BOLD) and CBF sensitized fMRI techniques. During each vascular challenge BOLD and CBF signals were determined simultaneously with a combined BOLD and flow-sensitive alternating inversion recovery (FAIR) pulse sequence. There was a good correlation between the global BOLD signal intensity changes during breath holding and CO(2) inhalation supporting the notion that the BHT is equivalent to CO(2) inhalation in evaluating the hemodynamic reserve capacity with BOLD fMRI. In contrast, there was no correlation between relative CBF changes during both vascular challenges, which was probably due to the reduced temporal resolution of the combined BOLD and FAIR pulse sequence.