Sodium T2*-weighted MR imaging of acute focal cerebral ischemia in rabbits

Changes in T2*-weighted tissue sodium (23Na) signal following acute ischemia may help to identify necrotic tissue and estimate the duration of ischemia. Sodium signal was monitored in a rabbit model of acute (0-4 h) focal cerebral ischemia, using gradient echo 23Na MR images (echo time = 3.2 ms) acquired continuously in 20-min intervals on a 4-Tesla MRI. 2,3,5-Triphenyl-tetrazolium chloride staining was used to identify regions of necrosis. In necrotic tissue, average 23Na image signal intensity decreased by 11% +/- 8% during the first 40 min of ischemia followed by a linear increase (0.19%/min) to 25% +/- 14% greater than baseline after 4 h of ischemia. The time course of 23Na signal change observed in necrotic tissue following focal ischemia in this rabbit model is consistent with an initial decrease in 23Na T2* relaxation time followed by an increase in tissue sodium concentration and provides further evidence that tissue 23Na signal may offer unique information regarding tissue viability that is complementary to other MR imaging techniques.     

A comparison of ferumoxytol with gadolinium as contrast agents for the diagnostic magnetic resonance imaging of osteomyelitis

BackgroundFerumoxytol, an FDA-approved superparamagnetic iron oxide nanoparticle (SPION) preparation used for the treatment of iron deficiency anemia, is also known to be taken up by macrophages in areas of infection or inflammation, where it produces negative contrast changes on T2-weighted MR images.PurposeWe sought to compare Ferumoxytol-induced MRI contrast changes with those observed using standard-of-care Gadolinium in patients presenting with symptoms suggestive of osteomyelitis.SubjectsOut of eighteen enrolled patients, 15 had MR imaging with both ferumoxytol and gadolinium. Based on clinical and/or pathologic criteria, 7 patients were diagnosed with osteomyelitis, 5 patients had osteomyelitis ruled out, and in 3 patients a definitive diagnosis could not be made.Field strength1.5 Tesla.SequencesUsed included STIR, T1-weighted and T2-weighted spin echo.AssessmentThe mean contrast changes upon ferumoxytol and gadolinium administration were measured from lesion regions of interest and compared with control regions.Statistical testsStudent's t-test, propagation of errors. Data are reported as means ± S.E.ResultsThe mean contrast changes, ΔC, associated with a diagnosis of osteomyelitis were found to be ΔCFe = −2.7 ± 0.7 when Ferumoxytol and T2w imaging sequences were used and ΔCGd = +3.1 ± 1.1 (P < 0.001) when Gadolinium and a T1w imaging sequence was used. The MRI contrast changes for both agents correlated with systemic markers of inflammation, such as the erythrocyte sedimentation rate. In patients without osteomyelitis, no significant contrast changes were observed in T2-weighted, Ferumoxytol-contrasted MRI. The macrophages in osteomyelitic lesions were found to take up at least 16 times as much iron as benign bone marrow.Data conclusionWe conclude that in terms of its MRI diagnostic accuracy for osteomyelitis Ferumoxytol-contrasted MRI is a promising approach for diagnosing osteomyelitis that merits further study.     

Pulse sequence optimization for T2-weighted MR imaging of the brain

The authors implemented bipolar velocity compensated pulse techniques for T2-weighted MR imaging of the brain. Signal-to-noise (S/N) and image quality was compared for pulse sequences with standard and optimized RF pulses, low and regular bandwidth versions and cardiac triggering. Images from bipolar velocity compensated sequences allowed better visualization of vessels and basilar cisterns and improved image quality relative to standard sequences without velocity compensation. The implementation of optimized RF pulses with bipolar sequences resulted in further improvement in image quality. Single echo sequences consistently had improved image quality and signal-to-noise relative to the second echo of a double echo sequence. Low bandwidth bipolar sequences with extended sampling period had 30% higher S/N, but at the cost of slight loss in edge definition. The highest image quality was obtained with the bipolar, optimized RF, single echo sequence. Using this technique contiguous high quality image slices could be obtained with velocity compensation. The addition of cardiac triggering to bipolar sequences resulted in slight improvement in image quality, but this difference was marginal and probably rarely necessary for MR imaging of the brain.     

Quantitative assessment of rat kidney function by measuring the clearance of the contrast agent Gd(DOTA) using dynamic MRI

Magnetic resonance imaging (MRI) has been applied to assess kidney function in normal rats by monitoring the passage of the extracellular contrast agent GdDOTA. High-resolution images have been obtained using either the rapid acquisition with relaxation enhancement (RARE) or the snapshot pulse sequence. The latter was superior in anatomic definition due to the shorter echo delays used. The GdDOTA induced signal enhancements in the various renal structures were theoretically modeled and the results of the regression analysis then used to estimate local tissue concentrations in renal cortex, inner medulla and outer medulla/pelvis. The concentration-time curves in vena cava and renal cortex were similar and distinctly different from the ones in medulla and pelvis. This is reflected in the time-to-peak (TTP) values, which were TTP (blood) = 0.18 +/- 0.03 < TTP (cortex) = 0.26 +/- 0.05 < TTP (outer medulla) = 0.62 +/- 0.03 < TTP (inner medulla/pelvis) = 0.92 +/- 0.16 min. The initial tracer uptake rates depended linearly on the dose of GdDOTA administered, the value of the uptake rate in the cortex being significantly higher than those in the outer and inner medulla, which were identical within error limits. The initial medullar tracer uptake followed a first-order kinetics. The rate constant k(cl) = (dc[medulla]/dt)/c[cortex] = 3.4 +/- 0.5 min(-1) for the transition from cortex (predominantly blood signal) to medulla (predominantly urine) was considered a measure for the renal clearance. Intravenous administration of furosemide at doses 2.5, 5, and 10 mg/kg led to a dose-dependent decrease of k(cl). This reflects the inhibitory effect of the diuretic furosemide on medullary water resorption and thus the dilution of the GdDOTA in urine.     

Complementary use of T2-weighted and postcontrast T1- and T21-weighted imaging to distinguish sites of reversible and irreversible brain damage in focal ischemic lesions in the rat brain

The evolution of a photochemically induced cortical infarct was monitored using T₂-, postcontrast (GdDOTA) T₁-, and postcontrast (DyDTPA-BMA) T₂¹-weighted NMR imaging techniques. Data acquired with these different NMR imaging types were compared, both qualitatively and quantitatively. The T₂¹-weighted NMR images after sprodiamide injection (DyDTPA-BMA) were perfusion-weighted images that allowed the differentiation between several infarct-related areas in terms of different degrees of perfusion deficiency. No quantitative information on cerebral blood flow (CBF) was obtained. A clear distinction was made between areas with a complete lack of CBF located in the core of the lesion and temporary CBF insufficiencies in the rim surrounding this core. Concomitant observations on T₂-weighted and postcontrast T₁-weighted images revealed the same temporary rim characterized by an increased water content, and an intact blood-brain barrier (BBB), as well as by reduced perfusion. This rim appeared within the first hours after infarct induction, reached a maximum 24 h later, and lasted between 3–5 days, when its size gradually decreased until complete disappearance. These observations suggest the existence of an area at risk. Only on postcontrast T₁-weighted images, the core of the lesion remained visible during the whole experimental period (10 days) and reflected in all likelihood the irreversibly damaged ischemic central core. The combined application of different NMR imaging techniques when studying focal cerebral infarctions in the rat brain allowed us to distinguish, in terms of NMR characteristics, zones of reversible from irreversible brain damage and to estimate the severity of the damage. This might offer an appropriate experimental setup for the screening of cerebroprotective compounds.     

Single voxel vascular transport functions of arteries,capillaries and veins; and the associated arterial input function in dynamic susceptibility contrast magnetic resonance brain perfusion imaging

PurposeThe composite vascular transport function of a brain voxel consists of one convolutional component for the arteries, one for the capillaries and one for the veins in the voxel of interest. Here, the goal is to find each of these three convolutional components and the associated arterial input function.Pharmacokinetic modellingThe single voxel vascular transport functions for arteries, capillaries and veins were all modelled as causal exponential functions. Each observed multipass tissue contrast function was as a first approximation modelled as the resulting parametric composite vascular transport function convolved with a nonparametric and voxel specific multipass arterial input function. Subsequently, the residue function was used in the true perfusion equation to optimize the three parameters of the exponential functions.Deconvolution methodsFor each voxel, the parameters of the three exponential functions were estimated by successive iterative blind deconvolutions using versions of the Lucy-Richardson algorithm. The final multipass arterial input function was then computed by nonblind deconvolution using the Lucy-Richardson algorithm and the estimated composite vascular transport function.ResultsSimulations showed that the algorithm worked. The estimated mean transit time of arteries, capillaries and veins of the simulated data agreed with the known input values. For real data, the estimated capillary mean transit times agreed with known values for this parameter. The nonparametric multipass arterial input functions were used to derive the associated map of the arrival time. The arrival time map of a healthy volunteer agreed with known arterial anatomy and physiology.ConclusionClinically important new voxelwise hemodynamic information for arteries, capillaries and veins separately can be estimated using multipass tissue contrast functions and the iterative blind Lucy-Richardson deconvolution algorithm.     

Detection of focal liver lesions in unenhanced and ferucarbotran-enhanced magnetic resonance imaging: a comparison of T2-weighted breath-hold and respiratory-triggered sequences

Purpose

To investigate the image quality and detection rate of focal liver lesions by comparing a T2-weighted breath-hold single-shot sequence and a T2-weighted high spatial resolution fast spin-echo sequence with respiratory triggering via unenhanced and superparamagnetic iron oxide (SPIO)-enhanced liver imaging.

Materials and Methods

The study was approved by the local ethical review board; informed consent was waived. Liver-lesion contrast was measured and a qualitative consensus evaluation of image quality and lesion detection was performed in 42 consecutive patients using a 1.5-T MR system.

Results

The liver-lesion contrast was significantly higher (P<.05) for the respiratory-triggered sequence compared to the breath-hold sequence regarding unenhanced and SPIO-enhanced imaging. The respiratory-triggered sequences revealed significantly higher image quality scores as well as higher numbers of detected liver lesions compared to the breath-hold sequence on unenhanced and SPIO-enhanced imaging. The SPIO contrast did not significantly improve the number of detected lesions on the respective sequences (P>.05).

Conclusion

We find that respiratory-triggered fast spin-echo sequences produce a higher image quality and a more precise liver-lesion detection rate thereby justifying the increased acquisition time necessary for this method.     

MRI contrast agent for molecular imaging of the HER2/neu receptor using targeted magnetic nanoparticles

In this study, Trastuzumab modified Magnetic Nanoparticles (TMNs) were prepared as a new contrast agent for detecting HER2 (Human epidermal growth factor receptor-2) expression tumors by magnetic resonance imaging (MRI). TMNs were prepared based on iron oxide nanoparticles core and Trastuzumab modified dextran coating. The TMNs core and hydrodynamic size were determined by transmission electron microscopy and dynamic light scattering. TMNs stability and cytotoxicity were investigated. The ability of TMNs for HER2 detection were evaluated in breast carcinoma cell lines (SKBr3 and MCF7 cells) and tumor-bearing mice by MRI and iron uptake determination. The particles core and hydrodynamic size were 9 ± 2.5 and 41 ± 15 nm (size range: 15?C87 nm), respectively. The molar antibody/nanoparticle ratio was 3.1?C3.5. TMNs were non-toxic to the cells below the 30 ??g (Fe)/mL concentration and good stable up to 8 weeks in PBS buffer. TMNs could detect HER2 oncogenes in the cells surface with imagable contrast by MRI. The invivo study in mice bearing tumors indicated that TMNs possessed a good diagnostic ability as HER2 specific contrast agent by MRI. TMNs were demonstrated to be able to selectively accumulate in the tumor cells, with a proper signal enhancement in MRI T2 images. So, the complex may be considered for further investigations as an MRI contrast agent for detection of HER2 expression tumors in human.     

Repeatability of arterial input functions and kinetic parameters in muscle obtained by dynamic contrast enhanced MR imaging of the head and neck

BackgroundQuantification of pharmacokinetic parameters in dynamic contrast enhanced (DCE) MRI is heavily dependent on the arterial input function (AIF). In the present patient study on advanced stage head and neck squamous cell carcinoma (HNSCC) we have acquired DCE-MR images before and during chemo radiotherapy. We determined the repeatability of image-derived AIFs and of the obtained kinetic parameters in muscle and compared the repeatability of muscle kinetic parameters obtained with image-derived AIF's versus a population-based AIF.Materials and methodsWe compared image-derived AIFs obtained from the internal carotid, external carotid and vertebral arteries. Pharmacokinetic parameters (v_e, K^trans, k_ep) in muscle—located outside the radiation area—were obtained using the Tofts model with the image-derived AIFs and a population averaged AIF. Parameter values and repeatability were compared. Repeatability was calculated with the pre- and post-treatment data with the assumption of no DCE-MRI measurable biological changes between the scans.ResultsSeveral parameters describing magnitude and shape of the image-derived AIFs from the different arteries in the head and neck were significantly different. Use of image-derived AIFs led to higher pharmacokinetic parameters compared to use of a population averaged AIF. Median muscle pharmacokinetic parameters values obtained with AIFs in external carotids, internal carotids, vertebral arteries and with a population averaged AIF were respectively: v_e (0.65, 0.74, 0.58, 0.32), K^trans (0.30, 0.21, 0.13, 0.06), k_ep (0.41, 0.32, 0.24, 0.18). Repeatability of pharmacokinetic parameters was highest when a population averaged AIF was used; however, this repeatability was not significantly different from image-derived AIFs.ConclusionImage-derived AIFs in the neck region showed significant variations in the AIFs obtained from different arteries, and did not improve repeatability of the resulting pharmacokinetic parameters compared with the use of a population averaged AIF. Therefore, use of a population averaged AIF seems to be preferable for pharmacokinetic analysis using DCE-MRI in the head and neck area.     

Microimaging at 14 tesla using GESEPI for removal of magnetic susceptibility artifacts in T(2)(*)-weighted image contrast.

In magnetic resonance imaging (MRI), T(2)(*)-weighted contrast is significantly enhanced by extremely high magnetic field strength, offering broad potential applications. However, the T(2)(*)-weighted image contrast distortion and signal loss artifact arising from discontinuities of magnetic susceptibility within and around the sample are also increased, limiting utilization of high field systems for T(2)(*)-weighted contrast applications. Due to the B(0) dependence of the contrast distortions and signal losses, and the heterogeneity of magnetic susceptibility in biological samples, magnetic susceptibility artifacts worsen dramatically for in vivo microimaging at higher fields. Practical applications of T(2)(*)-sensitive techniques enhanced by higher magnetic fields are therefore challenged. This report shows that magnetic susceptibility artifacts dominate T(2)(*)-weighted image contrast at 14 T, and demonstrates that the GESEPI (gradient echo slice excitation profile imaging) technique effectively reduces or eliminates these artifacts at long TE in the highest field (14 T) currently available for (1)H imaging.     

A phase method of measuring the vibrational relaxation time for CO2 molecules

Conclusions The phase method can be applied to other compounds, but the choice of molecules and vibrational levels is restricted by the need for the level to have two allowed IR transitions. Also, the use of the method is restricted by the availability of strong IR sources.The phase method is analogous in concept to the spectrophone method [I] The advantage of the phase method is that it allows measurement of the lifetime for a single level no matter where it lies in the system of vibrational levels. Cascade transitions in deactivation (stepwise transformation of vibration energy to heat) greatly complicates the interpretation in the speetrophone method and essentially restricts its use to the first excited levels. Establishment of the phase zero is the main source of error in the spectrophone method and requires special calibration [5]. This problem has a simple solution in the phase method.In some cases the vibrational relaxation time can be determined from the amplitude dependence as affected by pressure, but this requires correction for the pressure dependence of the absorption coefficient for the exciting transition as well as that of the conditions for escape of the spontaneous emission through-out the vibration-rotation band.Translated from Zhurnal Prikladnoi Spektroskopii, Vol. 10, No. 2, pp. 252–255, February, 1969.     

A comparison of selected organic tracers for quantitative scalar imaging in the gas phase via laser-induced fluorescence

Single crystal of La₃Ga_5.5Ta_0.5O₁₄ (LGT) containing intentionally 0.5 % of Ho³⁺ and 1 % of Yb³⁺ was grown by the Czochralski method. Examination of chemical composition of the grown crystal revealed that luminescent holmium and ytterbium ions are preferably retained in the melt and their actual concentrations are 0.12 and 0.24 %, respectively. Spectroscopic investigation performed encompassed IR host absorption spectra and Raman spectra at room temperature, optical absorption and luminescence spectra of Ho³⁺ and Yb³⁺ at room temperature and at 5 K, and luminescence decay curves at room temperature. It was found that all spectral bands recorded show important inhomogeneous line broadening. This feature was attributed to structural disorder inherent to the crystal lattice in which pentavalent Ta⁵⁺ ions occupy octahedral Ga(1) sites together with trivalent Ga³⁺ ions. Despite small concentrations of luminescent ions, the occurrence of nonradiative interaction that feeds the ⁵I₆ and ⁵I₇ levels of Ho³⁺ ions by transfer of an excitation from the ²F_5/2 level of Yb³⁺ ions was evidenced. Based on examination of spectroscopic parameters evaluated, it was concluded that LGT:Ho, Yb may be considered as a potential intermediate-gain laser active material able to emit infrared radiation from the ⁵I₇ → ⁵I₈ transition of Ho³⁺ around 2 micrometres upon laser-diode pumping into Yb³⁺ absorption band.     

The oral administration of MnCl2: A potential alternative to IV injection for tissue contrast enhancement in magnetic resonance imaging

Mn⁺² (as MnCl₂) was administered to rabbits intravenously and orally (a route of administration which based upon our previous experiments in rats⁷ promises to give selective hepatobiliary enhancement with less systemic toxicity). Nuclear magnetic relaxation dispersion or T₁ (NMRD) was performed on selected tissues (heart, liver, kidney, serum, and bile) in both animal groups to examine possible qualitative and semiquantitative differences in T₁ relaxation at equivalent sacrifice times. One animal was given an oral dose of MnCl₂ (620 micromoles/kg) and imaged sequentially (T₁ weighted sequence, .12T) for 30 minutes. The NMRD curves for organ tissues show an increase in relaxation efficacy in the 10–20MHz range characteristic of Mn-macromolecular complexes and are similar irrespective of the route of administration. The lack of increased relaxation enhancement for bile in this frequency range reflects cleavage of this complex upon excretion. Decreased overall relaxation in the liver is observed when oral Mn⁺² is compared to IV Mn⁺² due to the small fraction of administered dose that is absorbed. However, the images document a significant increase in the intensity of liver signal after the oral dose. We suspect this dose may ultimately be adjusted downward to give selective hepatobiliary effects.     

Conventional high resolution versus fast T(2)-weighted MR imaging of the heart: assessment of reperfusion induced myocardial injury in an animal model

Cardiac image quality in terms of spatial resolution and signal contrast was assessed for conventional and newly developed T(2)-weighted fast spin-echo imaging with high k-space segmentation. The capability in revealing regional myocardial edema and cellular damage was examined by a porcine model using histopathologic correlation. Twelve porcine hearts were excised from slaughtered animals and instantly perfused with 1000 mL cold cardioplegic solution. After 4 h of cold ischemia the hearts were reperfused for one hour using a "Langendorff" perfusion model followed by MR imaging at 1.5 Tesla. Three additional pig hearts served as controls and were studied by MR directly after harvesting. Histopathological analysis of regional tissue changes was performed macro- and microscopically. Short axis T(2)-weighted (3000/45 and 90) high quality fast spin-echo (FSE) images were recorded without cardiac action and signal intensity was correlated with histology. These images also served as gold standard for evaluation of newly developed faster sequences allowing measuring times shorter than 20 s. Fast T(2)-weighted imaging comprised single-slice fast spin echo (moderate echo train length of 23 echoes, FSE(m)), and multi-slice single-shot half-Fourier fast spin-echo (71 echoes, FSE(HASTE)) sequences, supplemented by versions with inversion recovery preparation (FSE(m)IR and FSE(HASTE)IR). Systolic function after reperfusion was restored in 10 porcine hearts. Tissue alterations included myocardial edema and contraction band necrosis which was found to be most severe in myocardium with maximum T(2) SI. Especially FSE(m) and FSE(m)IR sequences allowed differentiation of all categories of tissue damage on a high level of significance. In contrast, single-shot FSE(HASTE) and FSE(HASTE)IR sequences did not provide sufficient image quality to discriminate moderate and severe myocardial damage (p > 0.05). Different degrees of myocardial injury after ischemia and reperfusion can be staged by MR imaging, especially using conventional high resolution T(2)-weighted FSE sequences. The animal study indicates that fast T(2)-weighted FSE(m) and FSE(m)IR sequences lead to superior image quality and diagnostic accuracy compared to FSE(HASTE) and FSE(HASTE)IR imaging.     

A method for measuring the phase of the reflection coefficient in the visible range of the spectrum

A method for measuring the phase of the reflection coefficient in the optical wavelength range is proposed. The method is simple in experimental implementation and is based on measuring the energyreflection coefficients of a sample in two media with different refractive indices. Analytical and numerical estimates show that the measurement accuracy of the phase is on the order of 1°. The possibilities of using the results of the phase measurement in practice for a more complete characterization of materials and structures under investigation are considered.     

A comparison of three SPRITE techniques for the quantitative 3D imaging of the 23Na spin density on a 4T whole-body machine

Sodium density maps acquired with three SPRITE-based methods have been compared in terms of the resulting quantitative information as well as image quality and acquisition times. Consideration of factors relevant for the clinical implementation of SPRITE shows that the Conical-SPRITE variant is preferred because of a 20-fold reduction in acquisition time, slightly improved image quality, and no loss of quantitative information. The acquisition of a 3D data set (32x32x16; FOV=256x256x160 mm) for the quantitative determination of sodium density is demonstrated. In vivo Conical-SPRITE 23Na images of the brain of a healthy volunteer were acquired in 30 min with a resolution of 7.5x7.5x7.5 mm and a signal-to-noise ratio of 23 in cerebrospinal fluid and 17 in brain tissue.     

Unwrapping microcomputed tomographic images for measuring cortical osteolytic lesions in the 5T2 murine model of myeloma treated by bisphosphonate

Multiple myeloma is due to the proliferation of malignant plasma cells which increase the number of osteoclasts leading to trabecular and cortical bone osteolysis. The 5T2MM murine model reproduces the human disease and microcomputed tomography is a precise tool to investigate bone loss. Bisphosphonates (zoledronic acid or pamidronate) are used in preventing osteolysis. However, loss of cortical bone in not possible to quantify by histomorphometry on histological sections or microCT images.Osteolysis was studied in mice grafted with the 5THL subline to see if one drug was more active after 10 weeks. Mice were distributed into 4 groups: control, untreated, treated with pamidronate or with zoledronic acid. The left femurs were embedded undecalcified and sectioned at 7 μm. The right tibias and femurs were analyzed by microCT and trabecular morphometric parameters were obtained. Cortical bone osteolysis was analyzed by developing a new algorithm to unwrap microCT sections of the cortices, allowing measurement of the number of perforations, porosity and mean perforation area.The bisphosphonates had no significant effect on the tumor growth as evidence by the absence of effect on the M-protein level. Cortical perforations were evidenced on histological sections and their number seemed to be reduced by both bisphosphonates. MicroCT was used to quantify the trabecular bone: a bone loss was evidenced in the untreated myeloma group and both bisphosphonates appeared equal to preserve trabecular mass. However, the number and size of cortical perforations cannot be determined on 3D models. Unwrapping microCT images provided flat images allowing a precise determination of cortical perforations. Pamidronate did not reduce the number and size of cortical perforations but significantly reduced porosity. Zoledronic acid appeared significantly superior and considerably reduced all parameters.Unwrapping microCT image is a new method allowing the measurement of cortical perforations in bone malignancies, a parameter that cannot be measured correctly on 2D histological sections.     

A comparison of proton channeling in the <111> direction for BaF2 and CaF2

Protons in the region of 400 KeV have been used to study the channeling process in BaF₂ and CaF₂. The rate of loss of protons from the 111 linear channel, stopping power, and critical angle for the channel were found. Two techniques were employed, namely observationof elastic scattering by the lattice ions, and alpha particles produced by the reaction ¹⁹F(p,αy)¹⁶O, from the sharp resonance at 340 keV. Both techniques gave results in good agreement. The channel parameters were much closer together for the two crystals than had been anticipated on the basis of the large difference in charge between Ba and Ca.