Relative assessment of brain iron levels using MRI at 3 tesla

High field MR (magnetic resonance) images can be made sensitive to the relative concentration of tissue iron through the use ofT*₂-weighted contrast. This has enabled tissue iron levels to be assessed noninvasively by quantification of transverse relaxation rates. High field MRI may provide a new method to investigate neurological diseases which result in alteration of brain iron levels in specific areas of the human brain. Parkinson's disease (PD) results in an increase in iron concentration within the lateral region of the substantia nigra (SN), and provides one potential application of this methodology. Preliminary results of our findings are that there is a significant difference in SN iron levels in PD patients compared with age-matched controls, assessed by quantification of the reversible line-broadening component of transverse relaxation rate,R₂.     

A continuous-flow perfusion system for the maintenance and NMR study of small tissue samples in vitro

To describe and evaluate a novel perfusion system developed to maintain excised tissue in a flowing, oxygenated bathing solution during acquisition of nuclear magnetic resonance (NMR) data, and in addition allow precise data to be acquired continuously while altering the composition of the bathing solution surrounding the tissue. A chamber to house the tissue sample was constructed of interlocking sections of polyethylene tubing, and had approximate internal dimensions of 4 mm in diameter and 4 mm in height. Temperature-controlled, physiologically appropriate buffer solution was pumped via an infusion pump through the chamber, entering and exiting by way of small openings on either end. Immediately surrounding the polyethylene chamber was a tight-fitting four-loop solenoid RF coil. Measured proton NMR parameters were found to be fairly insensitive to the flow rate of the buffer if this coil was used only for reception and a larger-volume transmit-only coil was used for excitation. Temperature control of the sample was successfully implemented between 25 and 40°C. The perfusion system was found to be resistant to the effects of flow rate, as well as a useful tool for the administration of drugs or agents to the tissue. Changes in buffer composition could be performed on the fly without the need to reposition the sample each time a change was made. This avoidance of repositioning was found to yield a fivefold improvement in the precision of T₂ spectral parameters (using frog sciatic nerve as a sample).The authors wish to acknowledge the Canadian Institutes of Health Research (CIHR) for funding and the In Vivo NMR Facility of the University of Alberta for infrastructural support     

Changes in proton transverse relaxation times of rat myocardium that has suffered a previous oxidative insult

An oxidative insult can induce severe damage, as in the phenomenon of myocardial ischemia and reperfusion. However, there are situations in which the damage is not so obvious (e.g., silent ischemia or aging), and the negative effects will be seen only in time. Our aim was to reveal these small changes in the myofilaments by using the nuclear magnetic resonance (NMR) technique. We used Wistar rat hearts in a constant-pressure Langendorff system, perfused with oxygenated Krebs-Henseleit buffer at 37°C. After 15 minutes of stabilization, the hearts were perfused with buffer supplemented with H₂O₂ at 50, 75, or 100 μmol/L for 15 or 30 minutes. Fifteen-minute and 45-minute perfusion controls and unperfused hearts were also collected. Heart rate (HR) and left ventricular developed pressure (LVDP) were determined with the help of a latex balloon, inserted in the left ventricle and connected with a pressure transducer. Proton transverse relaxation times (T ₂) were determined at the end of the experiment.T ₂ values were measured again in the same tissue fragments after they had been glycerinated and incubated in relaxation and rigor media. The functional parameters (HR, LVDP, coronary flow) were not significantly changed in control and 50 μmol/L H₂O₂ groups but were increased in the 75 μmol/L H₂O₂ group and significantly decreased in the 100 μmol/L H₂O₂ group.T ₂ is significantly decreased in rigor media starting with 50 μmol/L H₂O₂ administrated for 30 minutes and does not correlate with dose and duration of the oxidative insult.T ₂ in rigor is shorter than in relaxation media within the groups, and this difference is increased in the treated hearts.     

Tissue oxygen tension measurements in the Shionogi model of prostate cancer using 19 F MRS and MRI

Objectives: To investigate changes in tumour tissue oxygenation throughout the tumour growth–regression–relapse cycle in an androgen-dependent animal tumour model. Materials and methods: ¹⁹F T₁ relaxometry of Perfluoro-15-Crown-5-Ether was used to measure in vivo partial oxygen pressure (pO₂) of Shionogi tumours on a 2.35-T MR scanner. Perfluoro-15-Crown-5-Ether was administered as an emulsion injected intravenously or as a neat compound injected directly into the tumour. Non-localized, tumour ¹⁹F T₁ measurements, made at multiple time points throughout the tumour cycle, were translated into pO₂ levels. Results: No correlation between tumour size and pO₂ values was found. Values of pO₂ for growing tumours (50 ± 30 torr) were significantly lower than for regressing and relapsing tumours after 9 days post-castration (70 ± 10 torr, p<0.05). Maximum pO₂ values (90 ± 30 torr) were reached between fifth and eighth day post-castration, when tumour pO₂ was significantly higher than both pre-castration (p<0.001) and after 9 days post-castration (p<0.05). Conclusion: We demonstrate that longitudinal pO₂ measurements in vivo are feasible. Values of pO₂ for growing androgen-dependent tumours were significantly lower than for regressing and relapsing androgen-independent tumours. These results have potential clinical importance in optimizing the timing of chemotherapy and/or radiotherapy of hormone dependent tumours.     

Quantitative T 2 measurement of a single voxel with arbitrary shape using pinwheel excitation and CPMG acquisition

Objective The aim of this study is to present a new approach for making quantitative single-voxel T ₂ measurements from an arbitrarily shaped region of interest (ROI), where the advantage of the signal-to-noise ratio (SNR) per unit time of the single-voxel approach over conventional imaging approach can be achieved. Materials and methods Two-dimensional (2D) spatially selective radiofrequency (RF) pulses are proposed in this work for T ₂ measurements based on using interleaved spiral trajectories in excitation k-space (pinwheel excitation pulses), combined with a summed Carr–Purcell Meiboom–Gill (CPMG) echo acquisition. The technique is described and compared to standard multi-echo imaging methods, on a two-compartment water phantom and an excised brain tissue. Results The studies show good agreement between imaging and our method. The measured improvement factors of SNR per unit time of our single-voxel approach over imaging approach are close to the predicted values. Conclusion Measuring T ₂ relaxation times from a selected ROI of arbitrary shape using a single-voxel rather than an imaging approach can increase the SNR per unit time, which is critical for dynamic T ₂ or multi-component T ₂ measurements.     

Data sampling in MR relaxation

Four time spacing methods for the sampling of magnetic resonance relaxation data are investigated: linear, logarithmic, geometric with time offset, and pure geometric spacing methods. They are compared with the respective normalized root-mean-square errors of the four parameters of biexponential inversion recoveries. Linear spacing was found to be inappropriate for NMR. Geometric spacing may be the method of choice to detect an unexpected exponent when sampling is performed from 1/28.7 of the shortest time constant up to five times the longest one.     

Aqueous urea as a model system for bi-exponential relaxation

Object To evaluate the utility of aqueous urea, doped inner- and outer-sphere relaxation agents, as an adjustable two-component model system. Materials and Methods T₂ was measured from 12 molal urea mixtures at pH 7.0 with varying amounts of the MnCl₂ and FeO_1.44 (Feridex^®, Berlex Inc, Montville, NJ). Results Bi-exponential relaxation was observed, with rates that were bilinearly related to [MnCl₂] and [FeO_1.44]. FeO_1.44 had comparable relaxivities on both urea and water, while MnCl₂ relaxivity was >  15x larger for water than for urea. Conclusion Aqueous urea, doped with inner- and outer-sphere contrast agents, is a two-compartment model system, which can be exhibit a wide range of different T₂s and signal fractions.     

Contrast-modified gradient echo imaging using rotary echo preparatory pulses

The use of on-resonance binomial composite pulses in two- or three-dimensional magnetization-prepared gradient-recalled echo magnetic resonance imaging experiments generates rotary echoes, leading to an increase in contrast range that is, in part, determined by the ratio ofT ₂ toT ₁. In comparison with other fast gradient-recalled echo imaging techniques designed for enhancedT ₂ contrast, this method is more robust with respect to radiofrequency field inhomogeneity and less sensitive with respect to motion artifacts. Three-dimensional parametric images may be calculated using least-squares fitting based on a simple model for steady-state longitudinal magnetization during the imaging sequences.     

Measurements of T1 and T2 relaxation times of colon cancer metastases in rat liver at 7 T

The purpose of this study was to investigate the magnetic resonance imaging (MRI) characteristics of colon cancer metastases in rat liver at 7 T. A dedicated RF microstrip coil of novel design was built in order to increase the signal-to-noise ratio and, in combination with respiratory triggering, to minimize motion artifacts. T₁- and T₂-weighted MR imaging was performed to follow tumor growth. T₁-weighted images provided a good anatomical delineation of the liver structure, while the best contrast between metastases and normal liver tissue was achieved with T₂-weighted images.Measurements of T₁ and T₂ relaxation times were performed with inversion recovery FLASH and Carr–Purcell–Meiboom–Gill and inversion recovery FLASH imaging sequences, respectively, for quantitative MR characterization of metastases. Both the T₁ and T₂ of the metastases were significantly higher than those of normal liver tissue. Further, an increase in the T₁ relaxation time of the metastases was observed with tumor growth. These findings suggest that quantitative in vivo MR characterization provides information on tumor development and possibly response to therapy, though additional studies are needed to elucidate the correlation between the changes in relaxation times and tumor microenvironment.     

Large increases in1H metaboliteT 2's after cerebral hypoxia-ischemia correlate with ATP depletion

In vivo proton (¹H) magnetic resonance spectroscopy (MRS) can measure cerebral metabolite concentrations and nuclear relaxation times. Function of the sodium (Na⁺)/potassium (K⁺) pump in cell membranes depends on adequate adenosine triphosphate (ATP) levels: intracellular Na⁺ is normally extruded in exchange for extracellular K⁺. Low ATP will cause pump dysfunction and loss of K⁺ accompanied by influx of Na⁺and water. Raised intracellular water may increase molecular mobility and this might be detectable as increased apparent transverse relaxation times (T ₂'s).¹H-MRS of the brains of newborn piglets during acute hypoxia-ischemia revealed enigmatic increases in the peak area of creatine + phosphocreatine (Cr) relative to those of choline-containing compounds (Cho) andN-acetylaspartate (NAA). Interleaved¹H and phosphorus (³¹P) MRS showed that theT ₂'s of both Cr and lactate (Lac) increased during acute hypoxia-ischemia and these changes correlated with reductions in nucleotide triphosphate (NTP; largely ATP). Within 50 h of metabolic recovery from the primary insult, as delayed energy failure developed, theT ₂'s of Cho, Cr, NAA, and Lac increased greatly. TheseT ₂ changes also correlated with NTP depletion. These observations demonstrate important relationships betweenT ₂'s and function of the ATP-dependent Na⁺/K⁺ pump.     

In vivo localized1 H spectroscopy of the rat eye at 7 T: preliminary studies

Preliminaryin vivo proton spectroscopic studies of the posterior chamber of the rat eye have been undertaken at 7 T. The Spatial and Chemical shift encoded Excitation (SPACE) localization sequence was used to acquire signals from 10-µl voxels and demonstrate the presence of metabolites associated with the vitreous humor, lens, retina, and the optic nerve. LocalizedT ₂ andT ₁ measurements of water in the vitreous humor indicate a relatively fluid environment. Susceptibility maps are used to demonstrate the difficulties ofin vivo spectroscopic investigations in the anterior regions of the eye. Comments are made concerning the implications for spectral resolution in these regions.     

Scaffold-aided repair of articular cartilage studied by MRI

OBJECTIVE: The objective of the study was to evaluate the ability of the noninvasive magnetic resonance techniques to monitor the scaffold-aided process of articular cartilage repair. MATERIALS AND METHODS: Defects of 4 mm in diameter and 3 mm in depth were created in right knees of 30 adolescent white New Zealand rabbits. Fourteen rabbits were implanted with poly(lactide-co-glycolic acid) (PLGA) scaffold trimmed to match the size and the shape of the defect (PLGA+ group). No procedure was applied to the remaining 16 animals (PLGA- group). Animals were sacrificed sequentially at 4, 12, and 24 weeks after the surgery and magnetic resonance T (2)-weighted images (400 MHz) of the dissected bone plugs at eight different echo times were taken to derive T (2) relaxation time. The images and the T (2) time dependencies versus the tissue depth were statistically analyzed. Histological results of bone plugs were evaluated using semiquantitative histological scales. RESULTS: The results obtained for PLGA repair tissue were evaluated versus the PLGA- group and the healthy tissue harvested from the opposite knee (reference group), and compared with histological results (hematoxylin and eosin staining). The magnetic resonance images and T (2) relaxation time profiles taken 4 weeks after surgery for both the PLGA- and PLGA+ group did not reveal the tissue reconstruction. After 12 weeks of treatment T (2) time dependence indicates a slight reconstruction for PLGA+ group. The T (2) time dependence obtained for PLGA+ samples taken after 24 weeks of treatment resembled the one observed for the healthy cartilage, indicating tissue reconstruction in the form of fibrous cartilage. The tissue reconstruction was not observed for PLGA- samples. CONCLUSION: The study revealed correlation between magnetic resonance and histology data, indicating the potential value of using MRI and spatial variation of T (2) as the noninvasive tools to evaluate the process of articular cartilage repair. It also suggested, that the PLGA scaffold-aided treatment could help to restore the proper architecture of collagen fibrils.     

Quantitative proton MRS of brain tumors reveals increased cholineT 2 in meningiomas

Quantitative proton spectroscopy was performed on 26 volunteers and 9 patients using STEAM. Voxels (8 ml) were localized within white matter or meningioma and water-suppressed spectra acquired with TR=2 s at three echo times. Concentrations were calculated using individual relaxation parameter values with tissue water as an internal reference. Compared to white matter, meningiomas were characterized by an increased choline/creatine ratio, the absence ofN-acetylasparate, and the presence of alanine. Further, theT ₂ of choline and its concentration were both significantly greater in meningiomas than white matter (p<0.01). Thus, the high choline/creatine ratio seen in meningioma spectra is the consequence of a greater concentration and a longerT ₂. The longerT ₂ may reflect differences in the relative proportions of choline-containing compounds. Our data demonstrate that individual measurements of relaxation parameters are important for long echo spectra and may reveal important metabolic information.     

单晶金电极的扫描隧道显微镜

扫描隧道显微镜可以在原子分辨率的基础上现场观察各种化学与物理现象.因此在表面化学领域得到广泛应用。由于制备容易并且抗污染能力强,单晶金成为扫描隧道显微镜研究的重要对象。简述了单晶金电极上面扫描隧道显微镜研究的基本现状。     

Quantification of metabolites from single-voxelin vivo 1H NMR data of normal human brain by means of time-domain data analysis

We present here a combination of time-domain signal analysis procedures for quantification of human brainin vivo ¹H NMR spectroscopy (MRS) data. The method is based on a separate removal of a residual water resonance followed by a frequency-selective time-domain line-shape fitting analysis of metabolite signals. Calculation of absolute metabolite concentrations was based on the internal water concentration as a reference. The estimated average metabolite concentrations acquired from six regions of normal human brain with a single-voxel spin-echo technique for theN-acetylaspartate, creatine, and choline-containing compounds were 11.4±1.0,6.5±0.5, and 1.7±0.2 mmol kg^–1 wet weight, respectively. The time-domain analyses ofin vivo ¹H MRS data from different brain regions with their specific characteristics demonstrate a case in which the use of frequency-domain methods pose serious difficulties.     

DynamicT 1 studies of gadolinium uptake in brain tumors using LL-EPI

Using ultrafastT ₁ mapping (LL-EPI), the uptake from a bolus injection of Gd-DO3A (ProHance) into the sagittal sinus and a brain tumor has been monitored. The measurement of absoluteT ₁ removes the possible error in uptake curves created fromT ₁-weighted sequences caused by changes inT ₂ ^* and simplifies the calculation of ProHance concentration. The LL-EPI sequence has an acquisition time of 1.2 s and is repeated every 4 s to obtain uptake curves with a high temporal and spatial resolution. Optimization of the LL-EPI sequence has been performed to obtain a precision of 5% over theT ₁ range 0.3–1.2 s.     

Contribution of various substrates to total citric acid cycle flux and ]anaplerosis as determined by13C isotopomer analysis and O2 consumption in the heart

A simple relationship between parameters derived from a¹³C NMR isotopomer analysis and O₂ consumption is presented that allows measurement of the absolute rate of acetyl-CoA oxidation and anaplerotic flux in tissues oxidizing a mixture of four substrates. The method was first applied in a study of the effects of work state and -adrenergic stimulation on net acetate oxidation and anaplerosis in the isolated working rat heart. The results demonstrate that the anticipated ratio of 2 between O₂ consumption and TCA cycle flux for hearts oxidizing only acetate holds at low workload when anaplerosis is low, but deviates toward a factor of 3 under high workload conditions when anaplerosis is increased. This analysis was also extended to hearts that oxidize a more physiological mixture of substrates including long-chain fatty acids, acetoacetate, lactate, pyruvate, and glucose. We show that the contribution each substrate makes to total TCA cycle flux can be determined by combined¹³C NMR and O₂ consumption measurements. The present study also demonstrates that stimulation of anaplerosis (by addition of propionate) can significantly alter the relative contribution each substrate makes to total TCA cycle flux. We conclude that if¹³C labeling patterns are selected appropriately, a comprehensive picture of flux through all major metabolic pathways feeding the cycle can be determined in a single experiment even when complex physiological mixtures of substrates are provided.     

An iron-based T 1 contrast agent made of iron-phosphate complexes: In vitro and in vivo studies

A new iron-based T ₁ contrast agent consisting of a complex of iron ions coordinated to phosphate and amine ligands (Fe_(phos) in short) has been characterized by spectroscopic and magnetic measurements. NMR relaxation studies showed r ₁ values to be dependent on the phosphate salt concentration, K₂HPO₄, present in the medium. r ₁ reaches a maximum value of 2.5 mM^?1 s^?1 for measurements carried out at 7 T and 298 K. ³¹P MRS, Mössbauer spectroscopy and magnetic measurements of Fe_(phos) solutions suggest paramagnetic Fe³⁺ ions present in the studied iron–phosphate complex. In vitro and in vivo toxicity experiments with C6 cells and CD1 mice, respectively, demonstrated lack of toxicity for Fe_(phos) at the highest dose tested in the MRI experiments (12 mM iron for C6 cells and 0.32 mmol iron/kg for mice). Finally, T ₁ weighted images of brain tumours in mice have shown positive contrast enhancement of Fe_(phos) for tumour afflicted regions in the brain.     

T2 Relaxation time study of the pig renal allografts

A previous study showed the possibility of the dependence of theT ₂ maps measured by Siemens Magnetom MR imager 1.5 T on the viability of the cadaveric kidney. For theT ₂ relaxometry study the pig model was used. Ten pig renal allografts were examined during 68 h after removal. Significant differences were found in the change of the initialT ₂ ⁱⁿⁱ values in the histogram within the first 20 h [₁=T ₂ ⁱⁿⁱ (2)–T ₂ ⁱⁿⁱ (20)] or 8 h [₂=T ₂ ⁱⁿⁱ (2)–T ₂ ⁿⁱ (8)] after removal between the groups of the damaged kidneys (₁=20.2±6.8 ms, ₂=19.4±3.0) and the kidneys without apparent damage (₁=9.4±8.5 ms, ₂=5.4±5.8).