Conventional MR imaging with simultaneous measurements of cerebral blood volume and vascular permeability in ganglioglioma

The conventional MR imaging appearance of gangliogliomas is often variable and nonspecific. Conventional MR images, relative cerebral blood volume (rCBV) and vascular permeability (K(trans)) measurements were reviewed in 20 patients with pathologically proven grade 1 and 2 gangliogliomas (n = 20) and compared to a group of grade 2 low-grade gliomas (n = 30). The conventional MRI findings demonstrated an average lesion size of 4.1 cm, contrast enhancement (n = 19), variable degree of edema, variable mass effect, necrosis/cystic areas (n = 8), well defined (n = 12), signal heterogeneity (n = 9), calcification (n = 4). The mean rCBV was 3.66 +/- 2.20 (mean +/- std) for grade 1 and 2 gangliogliomas. The mean rCBV in a comparative group of low-grade gliomas (n = 30), was 2.14 +/- 1.67. p Value < 0.05 compared with grade 1 and 2 ganglioglioma. The mean K(trans) was 0.0018 +/- 0.0035. The mean K(trans) in a comparative group of low-grade gliomas (n = 30), was 0.0005 +/- 0.001. p Value = 0.14 compared with grade 1 and 2 ganglioglioma. The rCBV measurements of grade 1 and 2 gangliogliomas are elevated compared with other low-grade gliomas. The K(trans), however, did not demonstrate a significant difference. Gangliogliomas demonstrate higher cerebral blood volume compared with other low-grade gliomas, but the degree of vascular permeability in gangliogliomas is similar to other low-grade gliomas. Higher cerebral blood volume measurements can help differentiate gangliogliomas from other low-grade gliomas.     

In vivo relaxation times of gray matter and white matter in spinal cord

In vivo relaxation times and relative spin densities of gray matter (GM) and white matter (WM) of rat spinal cord were measured. Inductively coupled implanted RF coil was used to improve the signal-to-noise ratio required for making these measurements. The estimated relaxation times (in milliseconds) are: T1(GM) = 1021+/-93, T2(GM) = 64+/-3.4, T1(WM) = 1089+/-126, and T2(WM) = 79+/-6.9. The estimated relative spin densities are: rho(GM) = (60+/-2.3)% and rho(WM) = (40+/-2.1)%. The T1 values of GM and white matter are not statistically different. However, the differences in T2 values and spin densities of GM and WM are statistically significant. These in vivo measurements indicate that the observed contrast between GM and WM in spinal cord MR images mainly arises from the differences in the spin density.     

An interleaved sampling strategy for MR spectroscopy in vivo: applications on human calf musculature

Assessment of relaxation times, magnetization transfer rates, or apparent diffusion coefficients by volume selective (1)H MR spectroscopy requires data from several single spectra with variable sequence parameters. Unintentional movements during the examination lead to inaccuracies, especially if the spatial distribution of concentrations is inhomogeneous. Improved comparability of the single spectra in a series recorded in vivo were obtained using a modified spectroscopic technique with INTerleaved ACquisiTion of multiple SPECtra (INTACTSPEC). INTACTSPEC series of spectra from the tibialis anterior muscle (m. tib. ant.), soleus muscle (m. soleus), and tibial bone marrow of 20 healthy volunteers were analyzed. Transverse relaxation times T(2) of methylene signals in muscular lipid stores ranged from 77 ms (intramyocellular methylene component in m. tib. ant.) to 88 ms (intramyocellular methylene component in m. soleus) and were similar to those from yellow tibial bone marrow (T(2) = 84 ms). Echo time-dependent signal intensities of choline and creatine deviated markedly from a monoexponential behavior in m. tib. ant., but were nearly exponential in m. soleus. Results from water diffusion measurements parallel and perpendicular to the axis of the lower leg showed significant differences between m. tib. ant. and m. soleus, probably due to the spatial orientation of the muscle fibers. Apparent diffusion coefficients along the leg axis were found to be higher in m. tib. ant. (2.10 +/- 0.08 x 10(-3) mm(2)/s) compared to m. soleus (1.78 +/- 0.11 x 10(-3) mm(2)/s), but m. soleus showed less restricted diffusion in perpendicular orientation (1.59 +/- 0.19 x 10(-3) mm(2)/s versus 1.20 +/- 0.08 x 10(-3) mm(2)/s in m. tib. ant.). Magnetization transfer experiments with various RF preparation pulse amplitudes led to very similar results for m. tib. ant. and m. soleus.     

A microstrip transmission line volume coil for human head MR imaging at 4T

A high-frequency RF volume coil based on the use of microstrip transmission line (MTL) has been developed for in vivo 1H MR applications on the human head at 4T. This coil is characterized by major advantages: (i) completely distributed coil circuit, (ii) high-quality factor (Q), (iii) simple coil structure, and (iv) better sensitivity and less signal-intensity variation in the MR image of the human head compared with an RF shielded birdcage coil of similar coil size. The proposed MTL volume coil does not require additional RF shielding for preventing Q degradation from radiation losses due to the unique MTL structure; thus, it provides a maximal useable space inside the volume coil when compared with most volume coils available at high fields with the same overall coil size. The intrinsic B(1) distribution of the MTL volume coil effectively compensates for the dielectric resonance effect at 4T and improves the signal homogeneity in human head MR images in the transaxial planes. The results of this study demonstrate that the MTL volume coil design provides an efficient and simple solution to RF volume coil design for human MR studies at high fields.     

MRI measurement of blood-brain barrier permeability following spontaneous reperfusion in the starch microsphere model of ischemia

Quantification of the acute increases in blood-brain barrier (BBB) permeability that occur subsequent to experimental ischemic injury has been limited to single time-point, invasive methodologies. Although permeability can be qualitatively assessed to visualise regional changes during sequential studies on the same animal using contrast-enhanced magnetic resonance imaging (MRI), quantitative information on the magnitude of change is required to compare barrier function during sequential studies on the same animal or between different animals. Recently, improvements in MRI tracer kinetic models and in MR hardware design mean that an estimate of permeability in vivo can now be obtained with acceptable accuracy and precision. We report here the use of such methods to study acute changes following spontaneous reperfusion in an animal model of ischemia. We have obtained estimates of BBB permeability following spontaneous reperfusion, subsequent to forebrain ischemia by unilateral carotid injection of starch microspheres in the rat. T2*-weighted and diffusion-trace imaging were used to monitor the initial reduction in CBF and the time-course of ischemia, respectively. Following reperfusion, an intraveneous bolus of dimeglumine gadopentetate (Gd-DTPA) and horseradish peroxidase (HRP) was given during a continuous acquisition of T1 maps with a 48 s temporal resolution. Permeability maps were constructed using a 4-compartment model; K(trans), the permeability-surface area product of the capillary walls was estimated to be 9.2 +/- 0.6 x 10(-4) min(-1) in the cortex. Visualisation of the regional extent of HRP extravasation on histological sections following termination of the experiment demonstrated very little correspondence to the region of Gd-DTPA leakage. Quantitative MRI assessment of BBB permeability following ischemia-reperfusion is consistent with published values obtained by invasive methods. Differences between Gd-DTPA-enhancement and HRP may reflect differences in the molecular size of the tracers.     

Characterizing blood volume fraction (BVF) in a VX2 tumor

OBJECTIVES: Neovascular proliferation of a tumor's blood supply is an important precursor of malignant growth. Evaluation of blood volume may provide useful information for the characterization, prognosis and response of tumors to therapy. The purpose of this study was to determine and compare the blood volume of tumor tissue measured noninvasively by MRI and microbubble contrast ultrasound imaging. MATERIALS AND METHODS: Twenty-two rabbits injected with VX2 tumors were studied. The blood volume fraction in tumor and muscle tissue was obtained from MRI T(1)-weighted images using a blood-pool agent, Clariscan, and by ultrasound using Definity and pulse inversion imaging. RESULTS AND CONCLUSIONS: Similar results were obtained from MRI and ultrasound. Estimation of the blood volume in tissue in the rim of a VX2 tumor 1.5 to 5.0 cm in diameter relative to that in the surrounding muscle was (mean+/-S.D.) 3.31+/-1.43 by MRI and 2.99+/-1.83 by ultrasound. The blood volume in the tissue relative to the total tissue volume (relative blood volume fraction) measured by MRI was 13+/-4.1% in tumor versus 4+/-1.4% in muscle (P<.01). Our data also suggested that, compared to the distribution volume of an extracellular contrast agent, Gd-DTPA, Clariscan as an intravascular agent demonstrated high-quality depictions of vascular structure of the tumor.     

A volume microstrip RF coil for MRI microscopy

Quantitative magnetic resonance imaging (MRI) studies of small samples such as a single cell or cell clusters require application of radiofrequency (RF) coils that provide homogenous B₁ field distribution and high signal-to-noise ratio (SNR).We present a novel design of an MRI RF volume microcoil based on a microstrip structure. The coil consists of two parallel microstrip elements conducting RF currents in the opposite directions, thus creating homogenous RF field within the space between the microstrips. The construction of the microcoil is simple, efficient and cost-effective.Theoretical calculations and finite element method simulations were used to optimize the coil geometry to achieve optimal B₁ and SNR distributions within the sample and predict parameters of the coil. The theoretical calculations were confirmed with MR images of a 1-mm-diameter capillary and a plant obtained with the double microstrip RF microcoil at 11.7 T. The in-plane resolution of MR images was 24 μm×24 μm.     

Quantitative, dynamic and noninvasive determination of skeletal muscle perfusion in mouse leg by NMR arterial spin-labeled imaging

Because mouse may relatively easily be genetically tailored to develop equivalent of human muscular diseases or to present controlled alterations of mechanisms involved in vasoregulation, it has become the prevalent species to explore such questions. However, the very small size of the animals represents a serious limitation when evaluating the functional consequences of these genetic manipulations. In this context, the recourse to arterial spin labeling (ASL) nuclear magnetic resonance (NMR) methods in which arterial water spins act as an endogenous and freely diffusible tracer of perfusion is tempting but challenging. This article shows that despite the small size of the animal, mouse muscle perfusion may be measured, at rest and in conditions of reactive hyperemia, using saturation inversion recovery sequence, a pulsed ASL variant, combined with NMR imaging. Baseline perfusion values in the mouse leg were 17+/-11 ml.min(-1).100 g(-1) (n=11) and were comparable to microsphere data from the literature. Under ischemia, leg perfusion was 1.2+/-9.3 ml.min(-1).100 g(-1) (n=11). The difference observed between basal and ischemic measurements was statistically different (P=.0001). The temporal pattern of hyperemia in mouse muscle was coherent with previously published measurements in humans and in rats. The mean peak perfusion was 62+/-24 ml.min(-1).100 g(-1) (n=6) occurring 48+/-27 s after the end of occlusion. In conclusion, this study demonstrated the ability of ASL combined to NMR imaging to quantify skeletal muscle perfusion in mice legs, both at rest and dynamically.     

Measurement of membrane hydraulic conductivity of bovine carotid artery endothelial cells using a perfusion microscope

The osmotic properties of bovine carotid artery endothelial cells (BCAECs) associated with cryobiology were investigated using a perfusion microscope. These properties include the hydraulic conductivity (Lp) and its activation energy (ELp). The response of isolated cells was observed when the extracellular concentration increased from 0.15 M to 0.5 M NaCl at three different temperatures. The transient volumes of the cell were calculated from the measurements of the projected areas with an assumption of a spherical cell. The hydraulic conductivity (Lp) and the osmotically inactive volume (Vb) of BCAECs were simultaneously determined using nonlinear regression to fit the change of cell volume estimated by water transport equations to measured cell volumes. The Lp values were 0.26 +/- 0.08, 0.12 +/- 0.02, and 0.06 +/- 0.02 m/atm/min (mean +/- SD) at 23, 11 and 4 degree C, respectively, yielding the activation energy of Lp of 47.6 kJ/mol according to the Arrhenius relationship.     

Ferrite-enhanced MRI monitoring in hyperthermia

In an MRI hyperthermia hybrid system, T₁ changes are investigated for monitoring thermal therapy at 0.2 T. The water bolus, which is needed for power transmission and cooling of the skin, limits MR image quality by signal compression and artifacts. Superparamagnetic ferrofluid in different concentration was investigated with MR relaxometry and MRI methods. We found that using ferrofluid in a low concentration of 70–90 ppm magnetite the water signal can be suppressed without susceptibility artifacts. With our method of signal suppression, a significant improvement of spatial and temporal resolution is possible. The ferrofluid is stable and allows RF heating at 100 MHz. This method of signal extinction may also be useful for other experimental setups where suppression of water is necessary.     

Sodium 3-D MRI of the human torso using a volume coil

Sodium MR imaging is considered to provide clinically important information about the human body that is not achievable by hydrogen-based approaches. However, due to the low natural abundance in biological tissues, sodium signals usually lead to low spatial resolution, low SNR, and long acquisition times compared to conventional 1H imaging, even using well-adapted surface coils. For our study, a volume coil was designed with nearly homogeneous excitation/receive characteristics and a suitable geometry fitting the human torso. A sufficient penetration throughout the entire thorax, abdomen, or pelvis is provided allowing for sodium imaging of the kidneys, the liver with gall bladder, or the myocardium. All measurements were performed on a 1.5 T whole body scanner using a spoiled 3-D gradient echo sequence. Imaging parameters TE, TR, and readout bandwidth were optimized for sensitive recording of the sodium component with slow transverse relaxation. Nonselective RF excitation pulses with a duration of 2.5 ms and rectangular shape were applied to avoid SAR problems. Narrow receiver bandwidth and excitation near the Ernst angle provided clinically practicable examinations with measuring times of less than 15 min at a spatial resolution of 8 x 8 x 8 mm3. Under these conditions, SNR of 11 for the kidneys and vertebral disks, 9 for the spinal canal, and 6 for the liver was achieved. A special 3-D spin echo sequence was used to determine T2, times which resulted to 15.3 +/- 1.1 ms for liver, 27.7 +/- 7.2 ms for kidneys, and 24.0 +/- 4.7 ms for the content of the spinal canal.     

Quantitative measurement of leakage volume and permeability in gliomas, meningiomas and brain metastases with dynamic contrast-enhanced MRI

The spatial properties and function of the tumor vasculature differ with the tumor type and grade. T1-weighted dynamic contrast-enhanced imaging technique enables the simultaneous quantification of some functional parameters of the vasculature. These are the fractional contrast-enhancing volumes of the tissue compartments (blood volume and leakage/extravascular extracellular volume) and the exchange parameters (perfusion and permeability). The relatively long monitoring duration of 12 min used here made it necessary to divide the extravascular extracellular compartment into two subcompartments, a slowly and a fast enhancing one with different permeabilities. Forty-one gliomas (WHO grades II-IV), six meningiomas and eight distant metastases were investigated. It was shown that the technique noninvasively provides information for separating different tumor types and characterizing their microenvironment. Fast permeability describes vessel permeability and was significantly increased in meningiomas as compared with intra-axial tumors. The corresponding volume of the fast enhancing compartment was significantly increased in meningiomas compared to all gliomas taken together. Slow permeability describes diffusion within the extravascular extracellular space and was significantly reduced in low-grade gliomas, indicating short diffusion distances. The slowly enhancing extravascular extracellular space was found to be increased in high-grade gliomas and distant metastases. Blood volume differed significantly among some tumor entities and glioma grades. Perfusion was shown to increase linearly with blood volume for volumes of up to 20%, flattening out thereafter. The scatter plots of extravascular extracellular volume and blood volume were shown to differ among the tumor entities.     

Quantitative evaluation of porous media wettability using NMR relaxometry

We propose a new method to determine wettability indices from NMR relaxometry. The new method uses the sensitivity of low field NMR relaxometry to the fluid distribution in oil-water saturated porous media. The model is based on the existence of a surface relaxivity for both oil and water, allowing the determination of the amount of surface wetted either by oil or by water. The proposed NMR wettability index requires the measurement of relaxation time distribution at four different saturation states. At the irreducible water saturation, we determine the dominant relaxation time of oil in the presence of a small amount of water, and at the oil residual saturation, we determine the dominant relaxation time of water in the presence of a small amount of oil. At 100% water and 100% oil saturation, we determine the surface relaxivity ratio. The interaction of oil with the surface is also evidenced by the comparison of the spin-lattice (T1) and spin-locking (T1rho) relaxation times. The new NMR index agrees with standard wettability measurements based on drainage-imbibition capillary pressure curves (USBM test) in the range [-0.3-1].     

RF coils for combined MR and hyperthermia studies: I. Hyperthermia applicator as an MR coil

Combining hyperthermia, an experimental/adjuvant therapeutic modality for cancer, with the non-invasive metabolic studies using Magnetic Resonance (MR) is an interesting area of research. This two parts article discusses the development and testing of a conventional RF hyperthermia applicator for MR studies and vice versa. In this first part, an inductive type applicator known as 'Magnetrode' in RF hyperthermia has been used both as an MR volume resonator and a surface coil. Its concurrent performance as an hyperthermic applicator and an MR transmit/receive coil has been evaluated.     

Magnetic resonance prediction of outcome after thrombolytic treatment

Treatment of clinical stroke with recombinant tissue plasminogen activator (rt-PA) carries the risk of hemorrhagic complications. Hence, predictors of therapeutic outcome with respect to (a) reperfusion and (b) tissue recovery would be very useful to identify potentially salvageable brain tissue. Magnetic resonance (MR) parameters, especially the apparent diffusion coefficient of water (ADC), perfusion-weighted imaging (PWI) and T(2) relaxometry are thought to provide this information. We evaluated the prognostic implications of ADC, PWI and T(2) relaxometry immediately before initiation of thrombolytic treatment in a model of clot embolism in rats. Animals (n = 14) were treated with intraarterial rt-PA (10 mg/kg) at 90 min after embolism. MR imaging was repeatedly performed at 4.7 T before and up to 5.5 h after embolism. ADC was calculated from diffusion-weighted images (b-values: 30, 765, 1500 s/mm(2)), arterial spin tagging was used for PWI, and quantitative T(2) relaxometry was performed with a Carr-Purcell-Meiboom-Gill (CPMG) sequence. A reperfusion index was calculated to assess the quality of thrombolytic recanalization. The decline of ADC at the end of the experiment to below 80% of control was defined as unfavorable outcome. The probability of tissue injury at the end of the experiments increased with the severity of ADC changes before the initiation of treatment (probability of unfavorable outcome: 21%, 44%, 65% for ADC values of 80-90%, 70-80% and <70% of control, respectively). Pretreatment PWI or T(2) relaxometry also correlated with outcome but-alone or in combination with pretreatment ADC maps-did not improve injury prediction over that obtained by ADC alone. Outcome was influenced positively by successful reperfusion the quality of which, however, could not be predicted by pre-treatment MR characteristics. The data demonstrate that ADC mapping performed before the initiation of thrombolytic treatment provides reliable risk assessment of impeding brain injury but due to uncertainties of postischemic reperfusion does not allow precise outcome prediction in individual experiments.     

Magnetic resonance imaging measurements of vascular permeability and extracellular volume fraction of breast tumors by dynamic Gd-DTPA-enhanced relaxometry

Vascular permeability (k(ep), min(-1)) and extracellular volume fraction (v(e)) are tissue parameters of great interest to characterize malignant tumor lesions. Indeed, it is well known that tumors with high blood supply better respond to therapy than poorly vascularized tumors, and tumors with large extracellular volume tend to be more malignant than tumors showing lower extracellular volume. Furthermore, the transport of therapeutic agents depends on both extracellular volume fraction and vessel permeability. Thus, before treatment, these tissue parameters may prove useful to evaluate tumor aggressiveness and to predict responsiveness to therapy and variations during cytotoxic therapies could allow to assess treatment efficacy and early modified therapy schedules in case of poor responsiveness. As a consequence, there is a need to develop methods that could be routinely used to determine these tissue parameters. In this work, blood-tissue permeability and extracellular volume fraction information were derived from magnetic resonance imaging dynamic longitudinal relaxation rate (R(1)) mapping obtained after an intravenous bolus injection of Gd-DTPA in a group of 92 female patients with breast lesions, 68 of these being histologically proven to be with carcinoma. For the sake of comparison, 24 benign lesions were studied. The measurement protocol based on two-dimensional gradient echo sequences and a monoexponential plasma kinetic model was that validated in the occasion of previous animal experiments. As a consequence of neoangiogenesis, results showed a higher permeability in malignant than in benign lesions, whereas the extracellular volume fraction value did not allow any discrimination between benign and malignant lesions. The method, which can be easily implemented whatever the imaging system used, could advantageously be used to quantify lesion parameters (k(ep) and v(e)) in routine clinical imaging. Because of its large reproducibility, the method could be useful for intersite comparisons and follow-up studies.     

Estimation of heat transfer and temperature rise in partial-body regions during MR procedures: an analytical approach with respect to safety considerations

In order to assess thermal response to RF exposure during MR procedures at the tissue level, simple analytical solutions to the non-stationary Pennes' bio-heat equation were obtained using the Green's function approach. Two thermal models appropriate for partial-body exposure were analyzed: In the first model, the temperature field at the periphery of an idealized volume RF resonator was modeled. The analytical solution reveals that tissue response to RF heating is characterized by an equilibration time and length. Both parameters are inversely related to tissue perfusion and vary for the soft-tissues considered between 0.27-25 min and 1.5-12 mm, respectively. None of the tissues investigated increase in temperature more than 0.5 degrees C for each W/kg of power dissipated. Secondly, a homogeneous tissue solution was derived that predicts the temperature-time course to an MR examination with time-varying specific absorption rates (SAR). Since SAR limits indicated in current MR safety standards relate to running SAR averages computed over an appropriate period of time, an expression was formulated that gives an upper limit for the temperature rise averaged over the same period of time, as a function of both the upper limit of running SAR averages and the duration of the MR examination. The analysis revealed that the partial-body SAR limits indicated in the IEC standard may not guarantee under all circumstances compliance with the basic restrictions concerning temperature rise.     

NMR relaxometry and imaging of water absorbed in biodegradable polymer scaffolds

Porous substrates made of poly(3-hydroxybutyrate-3-hydroxyvalerate) (PHBHV) were prepared by a particulate leaching method. After removing the salt by extraction in water, proton nuclear magnetic resonance (NMR) relaxometry and imaging were performed on sets of PHBHV substrates immersed in phosphate-buffered solution during 3 months at different time points. Polarized optical microscopy studies were performed on thin sections, 25 and 5 mum, of the PHBHV samples. The results of NMR relaxometry showed two (1)H nuclei populations, well distinguishable on the free induction decay (FID), due to the different decay time constants, a factor of 10(2) apart. Thus, it was possible to separate the two populations, giving separate distributions of T(1) relaxation times. One population could be associated with water protons in the pores and the other to macromolecular protons. The distributions of T(1) and T(2) of the water proton shifted to lower values with increasing immersion time to a constant value after 30 days. The results obtained by NMR imaging showed an initial increase in the apparent porosity, reaching a plateau after 25 days of immersion. This increase is attributed mainly to the absorption of water in the microporosity as supported by the results of the relaxometry measurements and shown by scanning electron microscopy. The average porosity measured by NMR imaging at the plateau, 78+/-3%, is slightly higher than that determined by optical microscopy, 73+/-9%, which may be due to the fact that the latter method did not resolve the microporosity. Overall, the results suggest that at early stages after immersing the scaffolds in the aqueous medium, first 30 days approximately, NMR imaging could underestimate the porosity of the substrate.     

Changes in the liver parenchyma after proton beam radiotherapy: evaluation with MR imaging

The objective of this study was to describe magnetic resonance (MR) findings with a 1.5T imager for hepatic parenchymal changes after proton beam radiotherapy. Thirty-two patients who received proton radiotherapy with doses of 50-87 Gy underwent MR imaging 1-75 months (mean 22 months) after the start of irradiation. Axial T(2), T(1)-weighted imaging, and a dynamic study after a gadolinium injection were performed. The irradiated areas showed hypointense in T(1)-weighted images, hyperintense in T(2)-weighted images, and intense and prolonged enhancement on the dynamic study (maximum relative enhancement 441.8%+/-263.3 vs. surrounding liver 145.6%+/-67.7, p<0.0001). T(2) values of the irradiated areas were 50.6 to 65.8 msec greater than in the surrounding liver (p<0.005). The values increased with time, being significantly greater 13 months or longer after the beginning of the therapy than after a period of less than 3 months (p<0.05). Pathologic examinations (n = 3) indicated that the irradiated areas were composed of collapsed lobules with hepatic small vein occlusions, and rich extracellular matrices which retained extracellular fluid. MR imaging can demonstrate hepatic parenchymal changes after proton beam radiotherapy, and show the changes are irreversible.