Blood oxygenation level-dependent (BOLD) total and extravascular signal changes and ΔR2* in human visual cortex at 1.5, 3.0 and 7.0 T

The characterisation of the extravascular (EV) contribution to the blood oxygenation level‐dependent (BOLD) effect is important for understanding the spatial specificity of BOLD contrast and for modelling approaches that aim to extract quantitative metabolic parameters from the BOLD signal. Using bipolar crusher gradients, total (b = 0 s/mm²) and predominantly EV (b = 100 s/mm²) gradient echo BOLD ΔR₂* and signal changes (ΔS/S) in response to visual stimulation (flashing checkerboard; f = 8 Hz) were investigated sequentially (within < 3 h) at 1.5, 3.0 and 7.0 T in the same subgroup of healthy volunteers (n = 7) and at identical spatial resolutions (3.5 × 3.5 × 3.5 mm³). Total ΔR₂* (z‐score analysis) values were ?0.61 ± 0.10 s^?1 (1.5 T), ?0.74 ± 0.05 s^?1 (3.0 T) and ?1.37 ± 0.12 s^?1 (7.0 T), whereas EV ΔR₂* values were ?0.28 ± 0.07 s^?1 (1.5 T), ?0.52 ± 0.07 s^?1 (3.0 T) and ?1.25 ± 0.11 s^?1 (7.0 T). Although EV ΔR₂* increased linearly with field, as expected, it was found that EV ΔS/S increased less than linearly with field in a manner that varied with TE choice. Furthermore, unlike ΔR₂*, total and EV ΔS/S did not converge at 7.0 T. These trends were similar whether a z‐score analysis or occipital lobe‐based region‐of‐interest approach was used for voxel selection. These findings suggest that calibrated BOLD approaches may benefit from an EV ΔR₂* measurement as opposed to a ΔS/S measurement at a single TE. Copyright © 2010 John Wiley & Sons, Ltd.     

Feasibility of noninvasive quantitative measurements of intrarenal R2′ in humans using an asymmetric spin echo echo planar imaging sequence

The purpose of this study was to demonstrate the feasibility of an asymmetric spin echo (ASE) single‐shot echo planar imaging (EPI) sequence for the noninvasive quantitative measurement of intrarenal R₂′ in humans within 20 s. The reproducibility of R₂′ measurements with the ASE‐EPI sequence was assessed in nine healthy young subjects in repeated studies conducted over three consecutive days. Moreover, we also evaluated whether the ASE‐EPI sequence‐measured R₂′ reflected the intrarenal oxygenation changes induced by furosemide in another group of normal human subjects (n = 10). Different flow attenuation gradients (b = 0, 40 and 80 s/mm²) were utilized to examine the impact of the intravascular signal contribution on the estimation of intrarenal R₂′. In the absence of flow dephasing gradients (b = 0 s/mm²), the computed coefficient of variation (CV) of R₂′ was 21.31 ± 4.52%, and the estimated R₂′ value decreased slightly, but not statistically significantly (p > 0.05), after the administration of furosemide in the medullary region. However, CV of R₂′ was much smaller in the presence of flow dephasing gradients (9.68 ± 3.58% with b = 40 s/mm²and 10.50 ± 3.62% with b = 80 s/mm²). Moreover, a significant reduction in R₂′ in the renal medulla was obtained (p < 0.05 for both b = 40 s/mm² and b = 80 s/mm²) after the administration of furosemide, reflecting an increase in oxygen tension in the medullary region. In addition, R₂′ measurements did not differ between the b = 40 s/mm² and b = 80 s/mm² scans, suggesting that small diffusion gradients were sufficient to minimize the intravascular signal contribution. In summary, we have demonstrated that renal R₂′ can be obtained rapidly using an ASE‐EPI sequence. The measurement was highly reproducible and reflected the expected intrarenal oxygenation changes induced by furosemide. Copyright © 2012 John Wiley & Sons, Ltd.     

Manipulation of cortical gray matter oxygenation by hyperoxic respiratory challenge: field dependence of R(2) * and MR signal response

The aim of this study was to quantitatively assess the field strength dependence of the transverse relaxation rate (R₂*) change in cortical gray matter induced by hyperoxia and hyperoxic hypercapnia versus normoxia in an intra‐individual comparison of young healthy volunteers. Medical air (21% O₂), pure oxygen and carbogen (95% O₂, 5% CO₂) were alternatively administered in a block‐design temporal pattern to induce normoxia, hyperoxia and hyperoxic hypercapnia, respectively. Local R₂* values were determined from three‐dimensional, multiple, radiofrequency‐spoiled, fast field echo data acquired at 1.5, 3 and 7 T. Image quality was good at all field strengths. Under normoxia, the mean gray matter R₂* values were 13.3 ± 2.7 s^–1 (1.5 T), 16.9 ± 0.9 s^–1 (3 T) and 29.0 ± 2.6 s^–1 (7 T). Both hyperoxic gases induced relaxation rate decreases ΔR₂*, whose magnitudes increased quadratically with the field strength [carbogen: –0.69 ± 0.20 s^–1 (1.5 T), –1.49 ± 0.49 s^–1 (3 T), –5.64 ± 0.67 s^–1 (7 T); oxygen: –0.39 ± 0.20 s^–1 (1.5 T), –0.78 ± 0.48 s^–1 (3 T), –3.86 ± 1.00 s^–1 (7 T)]. Carbogen produced larger R₂* changes than oxygen at all field strengths. The relative change ΔR₂*/R₂* also increased with the field strength with a power between 1 and 2 for both carbogen and oxygen. The statistical significance of the R₂* response improved with increasing B₀ and was higher for carbogen than for oxygen. For a sequence with pure T₂* weighting of the signal response to respiratory challenge, the results suggested a maximum carbogen‐induced signal difference of 19.3% of the baseline signal at 7 T and TE = 38 ms, but a maximum oxygen‐induced signal difference of only 3.0% at 1.5 T and TE = 76 ms. For 3 T, maximum signal changes of 4.7% (oxygen) and 8.9% (carbogen) were computed. In conclusion, the R₂* response to hyperoxic respiratory challenge was stronger for carbogen than for oxygen, and increased quadratically with the static magnetic field strength for both challenges, which highlights the importance of high field strengths for future studies aimed at probing oxygen physiology in clinical settings. Copyright © 2012 John Wiley & Sons, Ltd.     

Effect of respiratory hyperoxic challenge on magnetic susceptibility in human brain assessed by quantitative susceptibility mapping (QSM)

The purpose of this study was to measure the regional change of magnetic susceptibility in human brain upon inhalation of 100% oxygen by MRI quantitative susceptibility mapping (QSM). Fourteen healthy volunteers were scanned in a 3 T MR scanner with a 3D multi‐gradient‐echo sequence while breathing medical air (normoxia) and pure oxygen (hyperoxia). QSM images and R₂* maps were calculated. Mean susceptibility differences versus white matter were measured in regions of interest covering veins, gray matter (GM), and cerebrospinal fluid (CSF) under both conditions. Hyperoxia resulted in a strong susceptibility decrease in large veins (?154.4 ± 65.9 ppb, p < 10^?6), in a smaller reduction in GM (?1.3 ± 1 ppb, p < 0.001), and in a susceptibility increase in ventricular CSF (3.8 ± 1.8 ppb, p < 10^?5). The susceptibility decrease in veins implied an increase of venous oxygen saturation (SvO₂) by 10.1 ± 4.0%. Compared with QSM, R₂* was more seriously affected by long‐distance effects not related to local tissue oxygenation and increased in cerebral frontal regions (3 ± 2 s^?1, p < 0.0004) due to paramagnetic molecular oxygen in cavities. The results highlight the potential of QSM to yield region‐specific quantitative oxygenation information, and, thus, for applications such as oxygen‐therapy monitoring or identification of hypoxic tumor tissue during radiotherapy planning. Copyright © 2015 John Wiley & Sons, Ltd.     

Measurement of parenchymal extravascular R2* and tissue oxygen extraction fraction using multi‐echo vascular space occupancy MRI at 7 T

Parenchymal extravascular R₂* is an important parameter for quantitative blood oxygenation level‐dependent (BOLD) studies. Total and intravascular R₂* values and changes in R₂* values during functional stimulations have been reported in a number of studies. The purpose of this study was to measure absolute extravascular R₂* values in human visual cortex and to estimate the intra‐ and extravascular contributions to the BOLD effect at 7 T. Vascular space occupancy (VASO) MRI was employed to separate out the extravascular tissue signal. Multi‐echo VASO and BOLD functional MRI (fMRI) with visual stimulation were performed at 7 T for R₂* measurement at a spatial resolution of 2.5 × 2.5 × 2.5 mm³ in healthy volunteers (n = 6). The ratio of changes in extravascular and total R₂* (ΔR₂*) was used to estimate the extravascular fraction of the BOLD effect. Extravascular R₂* values were found to be 44.66 ± 1.55 and 43.38 ± 1.51 s^–1 (mean ± standard error of the mean, n = 6) at rest and activation, respectively, in human visual cortex at 7 T. The extravascular BOLD fraction was estimated to be 91 ± 3%. The parenchymal oxygen extraction fraction (OEF) during activation was estimated to be 0.24 ± 0.01 based on the R₂* measurements, indicating an approximately 37% decrease compared with OEF at rest. Copyright © 2014 John Wiley & Sons, Ltd.     

Rapid dynamic R1/R2*/temperature assessment: a method with potential for monitoring drug delivery

Local drug delivery by hyperthermia‐induced drug release from thermosensitive liposomes (TSLs) may reduce the systemic toxicity of chemotherapy, whilst maintaining or increasing its efficacy. Relaxivity contrast agents can be co‐encapsulated with the drug to allow the visualization of the presence of liposomes, by means of R₂*, as well as the co‐release of the contrast agent and the drug, by means of R_1, on heating. Here, the mathematical method used to extract both R₂* and R₁ from a fast dynamic multi‐echo spoiled gradient echo (ME‐SPGR) is presented and analyzed. Finally, this method is used to monitor such release events. R₂* was obtained from a fit to the ME‐SPGR data. Absolute R₁ was calculated from the signal magnitude changes corrected for the apparent proton density changes and a baseline Look–Locker R₁ map. The method was used to monitor nearly homogeneous water bath heating and local focused ultrasound heating of muscle tissue, and to visualize the release of a gadolinium chelate from TSLs in vitro. R₂*, R₁ and temperature maps were measured with a 5‐s temporal resolution. Both R₂*and R₁ measured were found to change with temperature. The dynamic R₁ measurements after heating agreed with the Look–Locker R₁ values if changes in equilibrium magnetization with temperature were considered. Release of gadolinium from TSLs was detected by an R₁ increase near the phase transition temperature, as well as a shallow R₂* increase. Simultaneous temperature, R₂* and R₁ mapping is feasible in real time and has the potential for use in image‐guided drug delivery studies. Copyright © 2014 John Wiley & Sons, Ltd.     

Effect of anesthesia on renal R2* measured by blood oxygen level‐dependent MRI

Blood oxygen level‐dependent (BOLD) MRI is increasingly being used to assess renal tissue oxygenation during disease based on the transverse relaxation rate (R₂*). In preclinical small animal models, the requisite use of anesthesia during imaging may lead to functional changes which influence R₂* and confound results. The purpose of this study was to evaluate the effects of four common anesthetic compounds on renal R₂* in healthy mice. Five female ICR mice were imaged with BOLD MRI approximately 25 min after induction with isoflurane (Iso; 1% or 1.5%, delivered in 100% O₂), ketamine/xylazine (KX), sodium pentobarbital (PB) or 2,2,2‐tribromoethanol (TBE). A significant effect of anesthetic agent on R₂* was observed in all tissue layers of the kidney, including the cortex, outer stripe of the outer medulla (OSOM), inner stripe of the outer medulla (ISOM) and inner medulla (IM). Pairwise significant differences in R₂* between specific agents were found in the cortex, OSOM and ISOM, with the largest difference observed in the ISOM between 1.5% Iso (26.6 ± 1.7 s^–1) and KX (66.0 ± 7.1 s^–1). The difference between 1% Iso and KX in the ISOM was not abolished when KX was administered with supplemental 100% O₂ or when 1% Iso was delivered in 21% O₂, indicating that the fraction of inspired oxygen did not account for the observed differences. Our results indicate that the choice of anesthesia has a large influence on the observed R₂* in mouse kidney, and anesthetic effects must be considered in the design and interpretation of renal BOLD MRI studies. Copyright © 2015 John Wiley & Sons, Ltd.     

Myelin water imaging and R2* mapping in neonates: Investigating R2* dependence on myelin and fibre orientation in whole brain white matter

R₂^* relaxation provides a semiquantitative method of detecting myelin, iron and white matter fibre orientation angles. Compared with standard histogram‐based analyses, angle‐resolved analysis of R₂^* has previously been shown to substantially improve the detection of subtle differences in the brain between healthy siblings of subjects with multiple sclerosis and unrelated healthy controls. Neonates, who are born with very little myelin and iron, and an underdeveloped connectome, provide researchers with an opportunity to investigate whether R₂^* is intimately linked with fibre‐angle or myelin content as it is in adults, which may in future studies be explored as a potential white matter developmental biomarker. Five healthy adult volunteers (mean age [±SD] = 31.2 [±8.3] years; three males) were recruited from Vancouver, Canada. Eight term neonates (mean age = 38.6 ± 1.2 weeks; five males) were recruited from the Children's Hospital of Chongqing Medical University neonatal ward. All subjects were scanned on identical 3 T Philips Achieva scanners equipped with an eight‐channel SENSE head coil and underwent a multiecho gradient echo scan, a 32‐direction DTI scan and a myelin water imaging scan. For both neonates and adults, bin‐averaged R₂^* variation across the brain's white matter was found to be best explained by fibre orientation. For adults, this represented a difference in R₂^* values of 3.5 Hz from parallel to perpendicular fibres with respect to the main magnetic field. In neonates, the fibre orientation dependency displayed a cosine wave shape, with a small R₂^* range of 0.4 Hz. This minor relationship in neonates provides further evidence for the key role myelin probably plays in creating this fibre orientation dependence later in life, but suggests limited clinical application in newborn populations. Future studies should investigate fibre‐orientation dependency in infants in the first 5 years, when substantial myelin development occurs.     

The role of iron and myelin in orientation dependent R2* of white matter

Brain myelin and iron content are important parameters in neurodegenerative diseases such as multiple sclerosis (MS). Both myelin and iron content influence the brain's R₂^* relaxation rate. However, their quantification based on R₂^* maps requires a realistic tissue model that can be fitted to the measured data. In structures with low myelin content, such as deep gray matter, R₂^* shows a linear increase with increasing iron content. In white matter, R₂^* is not only affected by iron and myelin but also by the orientation of the myelinated axons with respect to the external magnetic field. Here, we propose a numerical model which incorporates iron and myelin, as well as fibre orientation, to simulate R₂^* decay in white matter. Applying our model to fibre orientation‐dependent in vivo R₂^* data, we are able to determine a unique solution of myelin and iron content in global white matter. We determine an averaged myelin volume fraction of 16.02 ± 2.07% in non‐lesional white matter of patients with MS, 17.32 ± 2.20% in matched healthy controls, and 18.19 ± 2.98% in healthy siblings of patients with MS. Averaged iron content was 35.6 ± 8.9 mg/kg tissue in patients, 43.1 ± 8.3 mg/kg in controls, and 47.8 ± 8.2 mg/kg in siblings. All differences in iron content between groups were significant, while the difference in myelin content between MS patients and the siblings of MS patients was significant. In conclusion, we demonstrate that a model that combines myelin‐induced orientation‐dependent and iron‐induced orientation‐independent components is able to fit in vivo R₂^* data.     

Changes in the MR relaxation rate R(2)* induced by respiratory challenges at 3.0 T: a comparison of two quantification methods

The consistent determination of changes in the transverse relaxation rate R₂* (ΔR₂*) is essential for the mapping of the effect of hyperoxic and hypercapnic respiratory challenges, which enables the noninvasive assessment of blood oxygenation changes and vasoreactivity by MRI. The purpose of this study was to compare the performance of two different methods of ΔR₂* quantification from dynamic multigradient‐echo data: (A) subtraction of R₂* values calculated from monoexponential decay functions; and (B) computation of ΔR₂* echo‐wise from signal intensity ratios. A group of healthy volunteers (n = 12) was investigated at 3.0 T, and the brain tissue response to carbogen and CO₂–air inhalation was registered using a dynamic multigradient‐echo sequence with high temporal and spatial resolution. Results of the ΔR₂* quantification obtained by the two methods were compared with respect to the quality of the voxel‐wise ΔR₂* response, the number of responding voxels and the behaviour of the ‘global’ response of all voxels with significant R₂* changes. For the two ΔR₂* quantification methods, we found no differences in the temporal variation of the voxel‐wise ΔR₂* responses or in the detection sensitivity. The maximum change in the ‘global’ response was slightly smaller when ΔR₂* was derived from signal intensity ratios. In conclusion, this first methodological comparison shows that both ΔR₂* quantifications, from monoexponential approximation as well as from signal intensity ratios, are applicable for the monitoring of R₂* changes during respiratory challenges. Copyright © 2010 John Wiley & Sons, Ltd.     

Differences in iron and manganese concentration may confound the measurement of myelin from R1 and R2 relaxation rates in studies of dysmyelination

A model of dysmyelination, the Long Evans Shaker (les) rat, was used to study the contribution of myelin to MR tissue properties in white matter. A large region of white matter was identified in the deep cerebellum and was used for measurements of the MR relaxation rate constants, R₁ = 1/T₁ and R₂ = 1/T₂, at 7 T. In this study, R₁ of the les deep cerebellar white matter was found to be 0.55 ± 0.08 s ^–1 and R₂ was found to be 15 ± 1 s^–1, revealing significantly lower R₁ and R₂ in les white matter relative to wild‐type (wt: R₁ = 0.69 ± 0.05 s^–1 and R₂ = 18 ± 1 s^–1). These deviated from the expected ΔR₁ and ΔR₂ values, given a complete lack of myelin in the les white matter, derived from the literature using values of myelin relaxivity, and we suspect that metals could play a significant role. The absolute concentrations of the paramagnetic transition metals iron (Fe) and manganese (Mn) were measured by a micro‐synchrotron radiation X‐ray fluorescence (μSRXRF) technique, with significantly greater Fe and Mn in les white matter than in wt (in units of μg [metal]/g [wet weight tissue]: les: Fe concentration,19 ± 1; Mn concentration, 0.71 ± 0.04; wt: Fe concentration,10 ± 1; Mn concentration, 0.47 ± 0.04). These changes in Fe and Mn could explain the deviations in R₁ and R₂ from the expected values in white matter. Although it was found that the influence of myelin still dominates R₁ and R₂ in wt rats, there were non‐negligible changes in the contribution of the metals to relaxation. Although there are already problems with the estimation of myelin from R₁ and R₂ changes in disease models with pathology that also affects the relaxation rate constants, this study points to a specific pitfall in the estimation of changes in myelin in diseases or models with disrupted concentrations of paramagnetic transition metals. Copyright © 2016 John Wiley & Sons, Ltd.     

Spatial location and strength of BOLD activation in high-spatial-resolution fMRI of the motor cortex: a comparison of spin echo and gradient echo fMRI at 7 T

The increased blood oxygenation level‐dependent contrast‐to‐noise ratio at ultrahigh field (7 T) has been exploited in a comparison of the spatial location and strength of activation in high‐resolution (1.5 mm isotropic) gradient echo (GE) and spin echo (SE), echo planar imaging data acquired during the execution of a simple motor task in five subjects. SE data were acquired at six echo times from 30 to 55 ms. Excellent fat suppression was achieved in the SE echo planar images using slice‐selective gradient reversal. Threshold‐free cluster enhancement was used to define regions of interest (ROIs) containing voxels showing significant stimulus‐locked signal changes from the GE and average SE data. These were used to compare the signal changes and spatial locations of activated regions in SE and GE data. T₂ and T₂* values were measured, with means of 48.3 ± 1.1 ms and 36.5 ± 3.4 ms in the SE ROI. In addition, we identified a dark band in SE images of the motor cortex corresponding to a region in which T₂ and T₂* were significantly lower than in the surrounding grey matter. The fractional SE signal change in the ROI was found to vary linearly as a function of TE, with a slope that was dependent on the particular ROI assessed: the mean ΔR₂ value was found to be 0.85 ± 0.11 s^–1 for the SE ROI and ?0.37 ± 0.05 s^–1 for the GE ROI. The fractional signal change relative to the shortest TE revealed that the largest signal change occurred at a TE of 45 ms outside of the dark band. At this TE, the ratio of the fractional signal change in GE and SE data was found to be 0.48 ± 0.05. Phase maps produced from high‐resolution GE images spanning the right motor cortex were used to identify veins. The GE ROI was found to contain 18% more voxels overlying the venous mask than the SE ROI. Copyright © 2011 John Wiley & Sons, Ltd.     

Cerebral blood flow response to acute hypoxic hypoxia

Hypoxic hypoxia (inspiratory hypoxia) stimulates an increase in cerebral blood flow (CBF) maintaining oxygen delivery to the brain. However, this response, particularly at the tissue level, is not well characterised. This study quantifies the CBF response to acute hypoxic hypoxia in healthy subjects. A 20‐min hypoxic (mean P_ETo ₂ = 52 mmHg) challenge was induced and controlled by dynamic end‐tidal forcing whilst CBF was measured using pulsed arterial spin labelling perfusion MRI. The rate constant, temporal delay and magnitude of the CBF response were characterised using an exponential model for whole‐brain and regional grey matter. Grey matter CBF increased from 76.1 mL/100 g/min (95% confidence interval (CI) of fitting: 75.5 mL/100 g/min, 76.7 mL/100 g/min) to 87.8 mL/100 g/min (95% CI: 86.7 mL/100 g/min, 89.6 mL/100 g/min) during hypoxia, and the temporal delay and rate constant for the response to hypoxia were 185 s (95% CI: 132 s, 230 s) and 0.0035 s^–1 (95% CI: 0.0019 s^–1, 0.0046 s^–1), respectively. Recovery from hypoxia was faster with a delay of 20 s (95% CI: –38 s, 38 s) and a rate constant of 0.0069 s^–1 (95% CI: 0.0020 s^–1, 0.0103 s^–1). R₂*, an index of blood oxygenation obtained simultaneously with the CBF measurement, increased from 30.33 s^–1 (CI: 30.31 s^–1, 30.34 s^–1) to 31.48 s^–1 (CI: 31.47 s^–1, 31.49 s^–1) with hypoxia. The delay and rate constant for changes in R₂* were 24 s (95% CI: 21 s, 26 s) and 0.0392 s^–1 (95% CI: 0.0333 s^–1, 0.045 s^–1 ), respectively, for the hypoxic response, and 12 s (95% CI: 10 s, 13 s) and 0.0921 s^–1 (95% CI: 0.0744 s^–1, 0.1098 s^–1/) during the return to normoxia, confirming rapid changes in blood oxygenation with the end‐tidal forcing system. CBF and R₂* reactivity to hypoxia differed between subjects, but only R₂* reactivity to hypoxia differed significantly between brain regions. © 2013 The Authors. NMR in Biomedicine published by John Wiley & Sons, Ltd.     

Effects on upper airway collapsibility of presence of a pharyngeal catheter

Catheters that traverse the pharynx are often in place during clinical or research evaluations of upper airway function. The purpose of this study was to determine whether the presence of such catheters affects measures of upper airway collapsibility itself. To do so, pharyngeal critical closing pressure (Pcrit) and resistance upstream of the site of collapse Rus) were assessed in 24 propofol‐anaesthetized subjects (14 men) with and without a multi‐sensor oesophageal catheter (external diameter 2.7 mm) in place. Anaesthetic depth and posture were maintained constant throughout each study. Six subjects had polysomnography(PSG)‐defined obstructive sleep apnea (OSA) and 18 either did not have or were at low risk of OSA. Airway patency was maintained with positive airway pressure. At intervals, pressure was reduced by varying amounts to induce varying degrees of inspiratory flow limitation. The slope of the pressure flow relationship for flow‐limited breaths defined Rus. Pcrit was similar with the catheter in and out (?1.5 ± 5.4 cmH₂O and ?2.1 ± 5.6 cmH₂O, respectively, P = 0.14, n = 24). This remained the case both for those with PSG‐defined OSA (3.9 ± 2.2 cmH₂O and 2.6 ± 1.4 cmH₂O, n = 6) and those at low risk/without OSA (?3.3 ± 4.9 cmH₂O and ‐3.7 ± 5.6 cmH₂O, respectively, n = 18). Rus was similar with the catheter in and out (20.0 ± 12.3 cmH₂O mL^?1 s^?1 and 16.8 ± 10.1 cmH₂O mL^?1 s^?1, P = 0.22, n = 24). In conclusion, the presence of a small catheter traversing the pharynx had no significant effect on upper airway collapsibility in these anaesthestized subjects, providing reassurance that such measures can be made reliably in their presence.     

Quantitative BOLD response of the renal medulla to hyperoxic challenge at 1.5 T and 3.0 T

The aim of this study was to gage the magnitude of changes of the apparent renal medullary transverse relaxation time (ΔT₂*) induced by inhalation of pure oxygen (O₂) or carbogen (95% O₂, 5% CO₂) versus baseline breathing of room air. Eight healthy volunteers underwent 2D multi‐gradient echo MR imaging at 1.5 T and 3.0 T. Parametrical T₂* relaxation time maps were computed and average T₂* was measured in regions of interest placed in the renal medulla and cortex. The largest T₂* changes were measured in the renal medulla, with a relative ?T₂* of 33.8 ± 22.0% (right medulla) and 34.7 ± 17.6% (left medulla) as compared to room air for oxygen breathing (p > 0.01), and 53.8 ± 23.9% and 53.5 ± 33.9% (p < 0.01) for carbogen breathing, respectively at 3 T. At 1.5 T, the corresponding values were 13.7 ± 18.5% and 24.1 ± 17.1% (p < 0.01) for oxygen breathing and 23.9 ± 17.2% and 38.9 ± 37.6% (p < 0.01) for carbogen breathing. As a result, we showed that renal medullary T₂* times responded strongly to inhalation of hyperoxic gases, which may be attributed to the hypoxic condition of the medulla and subsequent reduction in deoxyhemoglobin. Copyright © 2012 John Wiley & Sons, Ltd.     

Fast volumetric imaging of bound and pore water in cortical bone using three‐dimensional ultrashort‐TE (UTE) and inversion recovery UTE sequences

We report the three‐dimensional ultrashort‐TE (3D UTE) and adiabatic inversion recovery UTE (IR‐UTE) sequences employing a radial trajectory with conical view ordering for bi‐component T₂* analysis of bound water (T₂*^BW) and pore water (T₂*^PW) in cortical bone. An interleaved dual‐echo 3D UTE acquisition scheme was developed for fast bi‐component analysis of bound and pore water in cortical bone. A 3D IR‐UTE acquisition scheme employing multiple spokes per IR was developed for bound water imaging. Two‐dimensional UTE (2D UTE) and IR‐UTE sequences were employed for comparison. The sequences were applied to bovine bone samples (n = 6) and volunteers (n = 6) using a 3‐T scanner. Bi‐component fitting of 3D UTE images of bovine samples showed a mean T₂*^BW of 0.26 ± 0.04 ms and T₂*^PW of 4.16 ± 0.35 ms, with fractions of 21.5 ± 3.6% and 78.5 ± 3.6%, respectively. The 3D IR‐UTE signal showed a single‐component decay with a mean T₂*^BW of 0.29 ± 0.05 ms, suggesting selective imaging of bound water. Similar results were achieved with the 2D UTE and IR‐UTE sequences. Bi‐component fitting of 3D UTE images of the tibial midshafts of healthy volunteers showed a mean T₂*^BW of 0.32 ± 0.08 ms and T₂*^PW of 5.78 ± 1.24 ms, with fractions of 34.2 ± 7.4% and 65.8 ± 7.4%, respectively. Single‐component fitting of 3D IR‐UTE images showed a mean T₂*^BW of 0.35 ± 0.09 ms. The 3D UTE and 3D IR‐UTE techniques allow fast volumetric mapping of bound and pore water in cortical bone. Copyright © 2016 John Wiley & Sons, Ltd.     

Diffusion tensor imaging of renal ischemia reperfusion injury in an experimental model

Renal ischemia reperfusion injury (IRI) is a major cause of acute renal failure. It occurs in various clinical settings such as renal transplantation, shock and vascular surgery. Serum creatinine level has been used as an index for estimating the degree of renal functional loss in renal IRI. However, it only evaluates the global renal function. In this study, diffusion tensor imaging (DTI) was used to characterize renal IRI in an experimental rat model. Spin‐echo echo‐planar DTI with b‐value of 300 s/mm² and 6 diffusion gradient directions was performed at 7 T in 8 Sprague‐Dawley (SD) with 60‐min unilateral renal IRI and 8 normal SD rats. Apparent diffusion coefficient (ADC), directional diffusivities and fractional anisotropy (FA) were measured at the acute stage of IRI. The IR‐injured animals were also examined by diffusion‐weighted imaging with 7 b‐values up to 1000 s/mm² to estimate true diffusion coefficient (D_true) and perfusion fraction (P_fraction) using a bi‐compartmental model. ADC of injured renal cortex (1.69 ± 0.24 × 10^?3 mm²/s) was significantly lower (p < 0.01) than that of contralateral intact cortex (2.03 ± 0.35 × 10^?3 mm²/s). Meanwhile, both ADC and FA of IR‐injured medulla (1.37 ± 0.27 × 10^?3 mm²/s and 0.28 ± 0.04, respectively) were significantly less (p < 0.01) than those of contralateral intact medulla (2.01 ± 0.38 × 10^?3 mm²/s and 0.36 ± 0.04, respectively). The bi‐compartmental model analysis revealed the decrease in D_true and P_fraction in the IR‐injured kidneys. Kidney histology showed widespread cell swelling and erythrocyte congestion in both cortex and medulla, and cell necrosis/apoptosis and cast formation in medulla. These experimental findings demonstrated that DTI can probe both structural and functional information of kidneys following renal IRI. Copyright © 2010 John Wiley & Sons, Ltd.     

EPR Investigations into the Kinetics of Trithiocarbonate‐Mediated RAFT‐Polymerization of Butyl Acrylate

Electron paramagnetic resonance (EPR) spectroscopy is used for measuring rate coefficients of addition, k_ad, and fragmentation, k_β, together with the associated equilibrium constants, K_eq, for butyl acrylate polymerizations mediated by S‐ethyl propan‐2‐ylonate‐S’‐propyl trithiocarbonate (EPPT) and by S‐S’‐bis(methyl‐2‐propionate) trithiocarbonate (BMPT). Experiments at ?40 °C yield k_ad = (3.4 ± 0.3) × 10⁶ L mol^?1 s^?1, k_β = (1.4 ± 0.4) × 10² s^?1, and K_eq = (2.6 ± 0.8) × 10⁴ L mol^?1 for EPPT and k_ad = (4.1 ± 0.9) × 10⁶ L mol^?1 s^?1, k_β = (4.5 ± 0.5) × 10¹ s^?1, and K_eq = (8 ± 4) × 10⁴ L mol^?1 for BMPT. The K_eq values are in satisfactory agreement with data from ab initio calculations.

     

Solvent effect on the propagation rate constant in the radical polymerization of bis(2-ethylhexyl) itaconate

Polymerization of bis(2-ethylhexyl) itaconate ( 1 ) with dimethyl azobis(isobutyrate) ( 2 ) was carried out at 50°C in various solvents. Polar solvents caused a significant decrease in the polymerization rate (R_p) and the molecular weight of resulting poly( 1 ). The propagating poly( 1 ) radical could be observed as a five-line ESR spectrum in the actual polymerization systems used. The stationary concentration of poly( 1 ) radical was determined by ESR to be 4,2–6,4 · 10^?6 mol · L^?1 at 50°C when the concentrations of 1 and 2 were 1,03 and 3,00 · 10^?2 mol · L^?1. Using R_p the monomer concentration and the polymer radical concentration, the propagation rate constant (K_p) was estimated to be 1,4–6,8 L · mol^?1 · s^?1, depending on the solvents used. The k_p value was smaller in more polar solvents. The solvent effect is explained in terms of the solvent affinity for the propagating polymer chain.     

Middle cerebral artery blood velocity during exercise with β‐1 adrenergic and unilateral stellate ganglion blockade in humans

A reduced ability to increase cardiac output (CO) during exercise limits blood flow by vasoconstriction even in active skeletal muscle. Such a flow limitation may also take place in the brain as an increase in the transcranial Doppler determined middle cerebral artery blood velocity (MCA V_mean) is attenuated during cycling with β‐1 adrenergic blockade and in patients with heart insufficiency. We studied whether sympathetic blockade at the level of the neck (0.1% lidocain; 8 mL; n=8) affects the attenuated exercise – MCA V_mean following cardio‐selective β‐1 adrenergic blockade (0.15 mg kg^?1 metoprolol i.v.) during cycling. Cardiac output determined by indocyanine green dye dilution, heart rate (HR), mean arterial pressure (MAP) and MCA V_mean were obtained during moderate intensity cycling before and after pharmacological intervention. During control cycling the right and left MCA V_mean increased to the same extent (11.4 ± 1.9 vs. 11.1 ± 1.9 cm s^?1). With the pharmacological intervention the exercise CO (10 ± 1 vs. 12 ± 1 L min^?1; n=5), HR (115 ± 4 vs. 134 ± 4 beats min^?1) and ΔMCA V_mean (8.7 ± 2.2 vs. 11.4 ± 1.9 cm s^?1) were reduced, and MAP was increased (100 ± 5 vs. 86 ± 2 mmHg; P < 0.05). However, sympathetic blockade at the level of the neck eliminated the β‐1 blockade induced attenuation in ΔMCA V_mean (10.2 ± 2.5 cm s^?1). These results indicate that a reduced ability to increase CO during exercise limits blood flow to a vital organ like the brain and that this flow limitation is likely to be by way of the sympathetic nervous system.