Jeff D. Winter

Quantification of renal perfusion: Comparison of arterial spin labeling and dynamic contrast‐enhanced MRI

To provide the first comparison of absolute renal perfusion obtained by arterial spin labeling (ASL) and separable compartment modeling of dynamic contrast‐enhanced (DCE) magnetic resonance imaging (MRI). Moreover, we provide the first application of the dual bolus approach to quantitative DCE‐MRI perfusion measurements in the kidney.

Sex differences in the human corpus callosum microstructure: A combined T2 myelin-water and diffusion tensor magnetic resonance imaging study

Sex differences in structure and organization of the corpus callosum (CC) have been identified in healthy adults and may be linked to distinct functional lateralization and processing in men and women. Magnetic resonance imaging (MRI) has facilitated noninvasive assessment of CC sex differences in morphology by volumetric imaging and microstructural organization by diffusion tensor imaging (DTI). Incorporation of recently developed myelin-water fraction (MWF) imaging may improve our understanding of CC sex differences. The aim of the current study was to combine DTI and diffusion tractography with MWF imaging to investigate CC sex differences in 22 healthy adults (11 male, 11 female). We performed MWF imaging using a 5-echo linear combination of spin echo images, and quantified mean diffusivity, axial diffusivity, radial diffusivity and fractional anisotropy (FA) by DTI. Fiber density index (FDi) was quantified using diffusion tractography. The MWF in males was significantly greater than females for the rostral body (p<0.05) and posterior midbody (p<0.005); whereas, the splenium MWF in males was significantly less than females (p<0.05). The DTI analysis revealed significantly increased FA in males compared with females within the genu of the CC (p<0.05). No significant sex-differences existed for mean diffusivity, axial diffusivity, radial diffusivity or FDi. Correlations between DTI parameters and MWF were significant but weak. Results of this study demonstrate regionally dependent sex differences in microstructural composition and organization of the CC and the lack of correlation between DTI and MWF suggest both measures provide unique information within the CC.

Normal tissue quantitative T1 and T2* MRI relaxation time responses to hypercapnic and hyperoxic gases.

RATIONALE AND OBJECTIVESnLongitudinal (T(1)) and effective transverse (T(2)*) magnetic resonance (MR) relaxation times provide noninvasive measures of tissue oxygenation. The objective for this study was to quantify independent effects of inhaled O(2) and CO(2) on normal tissue T(1) and T(2)* in rabbit liver, kidney, and paraspinal muscle.nnnMATERIALS AND METHODSnThree gas challenges (100% O(2), 10% CO(2) [balance air], and carbogen [90% O(2) + 10% CO(2)]) were delivered to the rabbits in random order to isolate the effects of inspired O(2) and CO(2). During each challenge, quantitative T(1) and T(2)* maps were collected on a 1.5 Tesla MR imaging. Mean changes in T(1) (ΔT(1)) and T(2)* (ΔT(2)*) were calculated from regions of interest in each organ.nnnRESULTSnGreatest ΔT(1) and ΔT(2)* changes were observed in liver for 10% CO(2) and in kidney for 100% O(2). ΔT(1) and ΔT(2)* generally followed predicted patterns when transitioning from air breathing: lower T(1)/higher T(2)* with inspired O(2), higher T(1)/lower T(2)* with inspired CO(2), and variable T(1)/T(2)* changes in the presence of both (ie, carbogen). New observations also emerged: 1) between-gas-challenge transitions revealed the greatest significance in ΔT(2)* for the liver and kidney resulting from the isolation of independent O(2) and CO(2) effects; 2) ΔT(2)* provided the best sensitivity and detected both tissue oxygenation and blood volume modulation; and 3) ΔT(1) sensitivity was restricted mainly to tissue oxygenation in the absence of counteracting vasodilatation.nnnCONCLUSIONnRobust use of MR relaxation times as noninvasive biomarkers requires an understanding of their relative sensitivity to organ-specific physiological responses.

Quantitative MRI assessment of VX2 tumour oxygenation changes in response to hyperoxia and hypercapnia

Magnetic resonance imaging (MRI) relaxation times provide indirect estimates of tissue O(2) for monitoring tumour oxygenation. This study provides insight into mechanisms underlying longitudinal (R(1) = 1/T(1)) and transverse effective (R(2)* = 1/T(2)*) relaxation rate changes during inhalation of 100% O(2) and 3%, 6% and 9% CO(2) (balanced O(2)) in a rabbit tumour model. Quantitative R(1), R(2)*, and dynamic contrast-enhanced (DCE) imaging was performed in six rabbits 12-23 days following implantation of VX2 carcinoma cells in the quadricep muscle. Invasive measurements of tissue partial pressure of O(2) (pO(2)) and perfusion were also performed, which revealed elevated pO(2) levels in all tumour regions for all hyperoxic gases compared to baseline (air) and reduced perfusion for carbogen. During 100% O(2) breathing, an R(1) increase and R(2)* decrease consistent with elevated pO(2) were observed within tumours. DCE-derived blood flow was weakly correlated with R(1) changes from air to 100% O(2). Further addition of CO(2) (carbogen) did not introduce considerable changes in MR relaxation rates, but a trend towards higher R(1) relative to breathing 100% O(2) was observed, while R(2)* changes were inconsistent. This observation supports the predominance of dissolved O(2) on R(1) sensitivity and demonstrates the value of R(1) over R(2)* for tissue oxygenation measures.

Noninvasive MRI Measures of Microstructural and Cerebrovascular Changes During Normal Swine Brain Development

The swine brain is emerging as a potentially valuable translational animal model of neurodevelopment and offers the ability to assess the impact of experimentally induced neurological disorders. The goal for this study was to characterize swine brain development using noninvasive MRI measures of microstructural and cerebrovascular changes. Thirteen pigs at various postnatal ages (2.3–43.5 kg) were imaged on a 1.5-Tesla MRI system. Microstructural changes were assessed using diffusion tensor imaging measures of mean diffusivity and fractional anisotropy. Cerebrovascular changes were assessed using arterial spin labeling measures of baseline cerebral blood flow (CBF) and the cerebrovascular reactivity (CVR) of the blood-oxygen level dependent (BOLD) MRI signal to CO2. We found a positive logarithmic relationship for regional tissue volumes and fractional anisotropy with body weight, which is similar to the pattern reported in the developing human brain. Unlike in the maturing human brain, no consistent changes in mean diffusivity or baseline CBF with development were observed. Changes in BOLD CVR exhibited a positive logarithmic relationship with body weight, which may impact the interpretation of functional MRI results at different stages of development. This animal model can be validated by applying the same noninvasive measures in humans.

Changes in Cerebral Oxygen Consumption and High-Energy Phosphates During Early Recovery in Hypoxic-Ischemic Piglets: A Combined Near-Infrared and Magnetic Resonance Spectroscopy Study

Near-infrared spectroscopy (NIRS) offers the ability to assess brain function at the bedside of critically ill neonates. Our group previously demonstrated a persistent reduction in the cerebral metabolic rate of oxygen (CMRO2) after hypoxia-ischemia (HI) in newborn piglets. The purpose of this current study was to determine the causes of this reduction by combining NIRS with magnetic resonance spectroscopy (MRS) to measure high-energy metabolites and diffusion-weighted imaging to measure cellular edema. Nine piglets were exposed to 30 min of HI and nine piglets served as controls. Proton and phosphorous MRS spectra, apparent diffusion coefficient (ADC) maps, and CMRO2 measurements were collected periodically before and for 5.5 h after HI. A significant decrease in CMRO2 (26 ± 7%) was observed after HI. Incomplete recovery of nucleotide triphosphate concentration (8 ± 3% <controls) and reduced ADC (16 ± 5%) suggested mitochondrial dysfunction. However, CMRO2 did not correlate with any metabolite concentration during the last 3 h of the recovery period, and no significant changes were found in phosphocreatine and lactate levels. Therefore, the CMRO2 decrease is likely a combination of impaired mitochondrial function and reduced energy demands during the acute phase, which has been previously observed in the mature brain.

Non-invasive accurate measurement of arterial PCO2 in a pediatric animal model.

The PCO2 in arterial blood (PaCO2) is a good parameter for monitoring ventilation and acid–base changes in ventilated patients, but its measurement is invasive and difficult to obtain in small children. Attempts have been made to use the partial pressure of CO2 in end-tidal gas (PetCO2), as a noninvasive surrogate for PaCO2. Studies have revealed that, unfortunately, the differences between PetCO2 and PaCO2 are too variable to be clinically useful. We hypothesized that end-inspiratory rebreathing, previously shown to equalize PetCO2 and PaCO2 in spontaneously breathing humans, would also be effective with positive pressure ventilation. Eight newborn Yorkshire pigs were mechanically ventilated via a partial rebreathing circuit to implement end-inspiratory rebreathing. Arterial blood was sampled and tested for PaCO2. A variety of alveolar ventilations resulting in different combinations of end-tidal PCO2 (30–50xa0mmHg) and PO2 (35–500xa0mmHg) were tested for differences between PetCO2 and PaCO2 (Pet-aCO2). The Pet-aCO2 of all samples was (meanxa0±xa01.96xa0SD) 0.4xa0±xa02.7xa0mmHg. Our study demonstrates that, in ventilated juvenile animals, end-inspiratory rebreathing maintains Pet-aCO2 to what would be a clinically useful range. If verified clinically, this approach could open the way for non-invasive monitoring of arterial PCO2 in critically ill patients.

High-contrast 3D neonatal brain imaging with combined T1- and T2-weighted MP-RAGE.

Optimization of magnetization‐prepared rapid gradient‐echo (MP‐RAGE) sequence variations for maximum white matter (WM) versus gray matter (GM) contrast in neonates at 3T was investigated. Numerical simulations were applied to optimize and compare three contrast preparation modules and to assess the effect of phase encoding (PE) order on contrast between WM and thin cortical GM layers. Simulations predict that a new sequence, which combines both T1‐ and T2‐weighting into the contrast preparation and utilizes an interleaved elliptical‐spiral PE order, should provide the strongest contrast between neonatal WM and cortical GM. This sequence was compared to a conventional MP‐RAGE acquisition (i.e., T1‐weighted preparation, centric PE order) for in vivo imaging of seven preterm newborn infants. Regional measurements of the contrast‐to‐noise ratio (CNR) between WM and GM demonstrated an increase of 50–70% (depending on GM region) using the new sequence, in good agreement with theoretical predictions. This improved contrast resulted in superior WM versus GM discrimination in intensity‐based brain tissue segmentations. Magn Reson Med 59:1190–1196, 2008.

Feasibility and precision of cerebral blood flow and cerebrovascular reactivity MRI measurements using a computer-controlled gas delivery system in an anesthetised juvenile animal model

To demonstrate the feasibility and repeatability of cerebrovascular reactivity (CVR) imaging using a controlled CO2 challenge in mechanically ventilated juvenile pigs.

Development of a composite material phantom mimicking the magnetic resonance parameters of the neonatal brain at 3.0 Tesla.

Objective:Development of a composite material phantom, comprised of polyvinyl alcohol cryogel (PVA-C) and an agarose additive, to effectively mimic the magnetic resonance relaxation times (T1 and T2) of neonatal white matter (WM) and gray matter (GM) at 3.0 T. Materials and Methods:Samples of PVA-C with and without agarose were prepared with 1 cycle of freezing/thawing. Measurements of T1 and T2, at 3.0 T, were performed on the samples at temperatures ranging from 20°C to 40°C. Results:A sample temperature of 40°C was required to achieve a T1 value sufficiently long to represent neonatal WM. At this temperature, neonatal WM relaxation times required 3% PVA-C with 0.3% agarose, whereas gray matter relaxation times required 8% PVA-C with 1.4% agarose. Conclusions:By adjusting the sample temperature, polyvinyl alcohol concentration, and agarose concentration, the relaxation times of neonatal brain tissues can be obtained using this composite material.