T2′‐ and PASL‐based perfusion mapping at 3 Tesla: influence of oxygen‐ventilation on cerebral autoregulation

Purpose:

To use T2′‐mapping together with Pulsed Arterial Spin Labeling (PASL) providing quantitative information of deoxygenation level and cerebral blood flow (CBF) in the cerebral gray matter to obtain simultaneous information about the cerebral oxygen metabolism and the resulting cerebral vasoreactivity under normoxic and hyperoxic conditions.

Materials and Methods:

Twelve young, healthy volunteers underwent MRI under normoxic and hyperoxic conditions performing PASL and high‐resolution, motion‐corrected T2* and T2‐mapping to calculate T2′values. Regions of interest (ROI) were placed in the frontoparietal cortex and thalamus by manual and automatic segmentation. For each ROI, mean normoxic T2′‐ and CBF values were extracted and compared with the same parameters assessed under hyperoxic ventilation.

Results:

A hyperoxic‐induced decrease of the CBF could be shown in the frontoparietal cortex (P = 0.009). The T2 values of frontoparietal cortex decreased under hyperoxic inhalation compared with normoxia (P = 0.01), whereas T2′ remained unchanged.

Conclusion:

Motion‐corrected high‐resolution T2′‐maps can be used together with PASL to evaluate the DeoxyHb content in relation to CBF in the cerebral gray matter. We could show that cortical CBF decreases under hyperoxic inhalation in healthy young subjects, whereas the T2′ values remained constant. These data suggest that hyperoxic‐induced vasoconstriction may protect the brain against hyperoxemia. J. Magn. Reson. Imaging 2012; 36:1347–1352. © 2012 Wiley Periodicals, Inc.     

Phantom studies simulating the impact of trabecular structure on marrow relaxation time,T2′

Phantom studies were conducted to investigate the impact of trabecular structure on the T₂′ signal measured by MRI. For a separation of density from structural effects, several phantoms were built. They consisted of parallel polyethylene strings arranged in a variety of different patterns to simulate (a) a constant uniform trabecular distribution with increasing trabecular thickness and (b) different structures with identical overall trabecular density. An asymmetric spin echo sequence was used to determine the apparent relaxation time T₂′. Changes in T₂′ are induced by susceptibility differences between the polyethylene strings simulating trabeculae and Gd-TPA doped saline simulating bone marrow. The results showed an increasing T₂′ decay rate with (a) decreasing spacing while the string density was constant and (b) with increasing string density while the string arrangement was constant. The results demonstrate that the T₂′ signal is affected not only by density but also by spatial distribution. However, the results also indicate that a separation of the two effects is not possible from a T₂′ measurement alone, but that e.g., a matching CT slice that would provide purely density information is additionally needed. Theoretical simulations confirmed these results.     

Imaging herpes viral thymidine kinase-1 reporter gene expression with a new 18F-labeled probe: 2'-fluoro-2'-deoxy-5-[18F]fluoroethyl-1-beta-d-arabinofuranosyl uracil

The preparation and radiolabeling of 2'-fluoro-2'-deoxy-1-beta-d-arabinofuranosyl-5-(2-fluoroethyl)-uracil (FFEAU) with 18F and its evaluation as a probe for imaging herpes simplex virus 1 thymidine kinase (HSV1-tk) gene expression are described. 2'-Fluoro-2'-deoxy-3',5'-di-O-benzoyl-1-beta-d-arabinofuranosyl-3-N-benzoyl-5-(2-[18F]fluoroethyl)-uracil 12 was prepared by nucleophilic substitution of the corresponding tosyl 8 or trifluoroethanesulfonyl 9 derivative with n-Bu4N[18F]F. Base hydrolysis was used to remove the benzoyl protecting groups, followed by HPLC purification, to afford [18F]FFEAU 13. The trifluoroethanesulfonyl substrate 9 appears to be the better labeling precursor. Carrier n-Bu4NF was added to the labeling reaction, which resulted in specific activities of 40-70 Ci/mmol (estimated). Radiochemical purity averaged 94+/-4%. Although [18F]FFEAU was obtained in low radiochemical yield with 9 and further optimization of the radiosynthesis will be required, sufficient product was available for a series of in vitro and in vivo studies. [18F]FFEAU was directly compared with [3H]TdR in a series of in vitro accumulation studies involving a HSV1-tk stably transduced cell line, RG2TK+ and a nontransduced, wild-type RG2 cells. The initial in vitro and in vivo imaging studies are promising; FFEAU has in vitro accumulation and sensitivity characteristics similar to that previously reported for FIAU, but greater selectivity than FIAU due to lower uptake and retention in nontransduced cells and tissues. The animal imaging experiment showed low levels of radioactivity in the lungs, with little or no radioactivity seen in the heart, liver, spleen and intestines.     

Quantification of myocardial strain at early systole in mouse heart: Restoration of undeformed tagging grid with single‐point HARP

Purpose:

To develop accurate strain and torsion quantification method for the assessment of myocardial contraction in mice by MRI tagging.

Materials and Methods:

Ventricular wall motion at baseline and during β‐adrenergic stimulation was assessed in mice using MRI tagging. Myocardial strain and torsion were quantified using finite element analysis method. A harmonic phase (HARP) based method was developed for the restoration of undeformed taglines for more accurate calculation of myocardial wall strain and torsion.

Results:

Myocardial deformation was observed at early systole (<20 msec after QRS) both at baseline and during β‐adrenergic stimulation. The HARP‐based method allowed robust restoration of undeformed taglines that can be used as the reference in finite element analysis of the tagged images. Without such correction for myocardial deformation in the reference image, inaccuracy in strain quantification underestimated significant strain development at early systole in dobutamine‐stimulated hearts.

Conclusion:

The HARP‐based method developed in the current study enabled automated restoration of undeformed taglines in mouse hearts, leading to more accurate calculation of myocardial wall strain and torsion during dobutamine stimulation. J. Magn. Reson. Imaging 2010;32:608–614. © 2010 Wiley‐Liss, Inc.     

2β-carbomethoxy-3β-(4- and 2-[F]fluoromethylphenyl)tropanes: specific probes for in vivo quantification of central dopamine transporter sites

Dopamine reuptake transporter binding kinetics of 2β-carbomethoxy-3β-(4-[¹⁸F]fluoromethylphenyl)tropane (p-FWIN) and 2β-carbomethoxy-3β-(2-[¹⁸F]fluoromethylphenyl)tropane (o-FWIN) were determined in vervet monkeys using positron emission tomography (PET). Ligand localization was rapid and specific to the striatum with kinetic estimates comparable with those of ¹¹C-labeled WIN 35,428 (CWIN). Binding was more specific with p-FWIN than with CWIN or o-FWIN. The relatively longer half-life of the ¹⁸F radiolabel enabled longer acquisition times with p-FWIN, resulting in less variability in the kinetic estimates.     

The individual and combined influence of ACE and ACTN3 genotypes on muscle phenotypes before and after strength training

Alternative measures of muscle size, strength, and power to those used in previous studies could help resolve the controversy surrounding associations between polymorphisms of the angiotensin‐I converting enzyme (ACE) and α‐actinin‐3 (ACTN3) genes and skeletal muscle phenotypes, and the responses to resistance training (RT). To this end, we measured quadriceps femoris muscle volume (V_m), physiological cross‐sectional area (PCSA), maximum isometric force (F_t), specific force (F_t per unit PCSA), maximum isoinertial strength (1‐RM), and maximum power (W_max; n = 40) before and after 9‐week knee extension RT in 51 previously untrained young men, who were genotyped for the ACE I/D and ACTN3 R577X polymorphisms. ACTN3 R‐allele carriers had greater V_m, 1‐RM, and W_max than XX homozygotes at baseline (all P < 0.05), but responses to RT were independent of ACTN3 genotype (all P > 0.05). Muscle phenotypes were independent of ACE genotype before (all P > 0.05) and after RT (all P > 0.01). However, people with the “optimal” ACE+ACTN3 genotype combination had greater baseline 1‐RM and W_max compared to those with the “suboptimal” profile (both P < 0.0125). We show for the first time that the ACTN3 R577X polymorphism is associated with human V_m and (independently and in combination with the ACE I/D polymorphism) influences 1‐RM and W_max.     

Map-ISODATA demarcates regional response to combination rt-PA and 7E3 F(ab')2 treatment of embolic stroke in the rat

PURPOSE: To investigate the ability of map-ISODATA (Iterative Self-Organizing Data Analysis Technique) to classify the different categories of ischemic damage in the lesion and to evaluate a combined (thrombolysis plus antiplatelet) treatment efficacy in an embolic stroke of rat. MATERIALS AND METHODS: Rats subjected to embolic stroke with (N=12) and without (N=10) rt-PA and 7E3 F(ab')2 treatment (4 hours after embolization) were followed (at 2, 24, and 48 hours post-MCAO) with magnetic resonance imaging (MRI) using T1, T2, and apparent diffusion coefficient of water (ADCw). ISODATA was computed from T1, T2, and ADCw maps. The signatures characterized by the map-ISODATA were compared with histological quantitative evaluation and were employed to demarcate the specific regions in the lesion. RESULTS: The signature described by map-ISODATA is highly correlated with the degree of tissue damage in the lesion and can distinguish the severity of ischemic tissue injury. Based upon map-ISODATA, ischemic lesion area can be divided into three specific regions, each characterized by a distinct evolution of injury and treatment response. The combined treatment significantly reduces the lesion size between 24 and 48 hours and improves the outcome 48 hours post-MCAO compared with the control group. CONCLUSION: Map-ISODATA provides an accurate means to identify lesion area, to distinguish ischemic damage, and to detect treatment response. 7E3 F(ab')2 extends the rt-PA treatment window to at least four hours after the onset of embolic stroke of rat.     

Impact of salbutamol on muscle metabolism assessed by 31P NMR spectroscopy

The potential ergogenic effects of oral salbutamol intake were demonstrated for decades but the underlying mechanisms remain to elucidate. We hypothesized that improved exercise performance after acute oral salbutamol administration is associated with changes in muscle metabolism. Twelve healthy, nonasthmatic, moderately trained, male subjects were recruited to compare in a double‐blind crossover randomized study, an oral dose of salbutamol (4 mg) and a placebo. After treatment administration, subjects performed repetitive plantar flexions to exhaustion in a 3T magnet. Continuous ³¹P nuclear magnetic resonance spectroscopy assessment of the calf muscles was performed at rest, during exercise, and during recovery. No significant difference between treatments was detected in metabolite concentration at rest (P > 0.05). Creatine phosphate and inorganic phosphate changes during and immediately after exercise were similar between treatments (P > 0.05). Intramuscular pH (pHi) was significantly higher at rest, at submaximal exercise but not at exhaustion with salbutamol (pHi at 50% of exercise duration, 6.8 ± 0.1/6.9 ± 0.1 for placebo and salbutamol, respectively, P < 0.05). The maximal power (28 ± 7 W/23 ± 7 W; P = 0.001) and total work (1702 ± 442 J/1381 ± 432 J; P = 0.003) performed during plantar flexions were significantly increased with salbutamol. Salbutamol induced significant improvement in calf muscle endurance with similar metabolic responses during exercise, except slight differences in pHi. Other mechanisms than changes in muscle metabolism may be responsible for the ergogenic effect of salbutamol administration.     

Relaxation of solvent protons by solute Gd3+-chelates,revisited

The magnetic field dependence (NMRD profile) of 1/T₁, of solvent protons in an aqueous solution of Gd(DTPA)^2? was remeasured at 5,15,25,30, and 35°C. The data were reanalyzed with the usual low-field theory, using recently published values for T_M, the residence lifetime of the single inner-coordinated waters of solute Gd(DTPA)^2?. (These T_M values are significantly longer than earlier estimates). Values were obtained for three dynamic parameters: T_R, the rotational relaxation time of solute ions, and T_SO and T_V, the low-field relaxation time of the Gd³⁺ magnetic moment and the related correlation time. These Gd(DTPA)²⁺ values, together with recent results for T_M for Gd(DTPA-BMA) — a nonionic structural analog of Gd(DTPA)^2? with an unusually long T_M — were used to calculate NMRD profiles at 5 and 35°C. These profiles agree very well with new data given here for a solution of Gd(DTPA-BMA). This reaffirms the importance of knowing the temperaturedependent values of T_M a priori in order to obtain unambiguous quantitative theoretical analyses of NMRD profiles of chelates of known structure. Additionally, the theory of inner sphere relaxation is extended to high fields, at which the magnetic energy of a solute moment is greater than its thermal energy.