Evaluation of nonionic nitroxyl lipids as potential organ-specific contrast agents for magnetic resonance imaging.

Considering their intrinsic properties of accumulation in the hepatic tissue, we have synthesized nitroxyl-containing lipids as potential organ-specific contrast agents for magnetic resonance imaging (MRI). Their resistance to reduction by ascorbate and in liver homogenates, and their relaxivity in different media were investigated and compared to those of free carboxyl-Proxyl (3-carboxy-2,2,5,5-tetramethylpyrrolidine-1-oxyl) and Tempamaine (4-amino-2,2,6,6-tetramethylpiperidine-1-oxyl). With respect to the reduction rates by ascorbate, the lipid derivatives show the same well-known order of reactivity as carboxy-Proxyl and Tempamine, the five-membered nitroxyls being more stable than the six-membered compounds. However the binding of the piperidinoxyl compounds to the fatty acids confers to those lipid derivatives a markedly increased stability. Similarly, in liver homogenates, the nitroxyl lipids remained unchanged more than 20 min, contrarily to carboxy-Proxyl and Tempamine. The measurements of spin-lattice relaxation time (T1) in biological media have demonstrated a higher relaxivity of nitroxyl lipids, which can be related to their interaction with proteins. Tested in vivo, one of the synthesized compounds (0.75 mmol/kg) produced an enhancement of 44 +/- 12% of the hepatic signal 5 min after intraportal injection in T1-weighted images. The potential applicability of the other nitroxyl lipids as contrast agents for MRI was limited in the in vivo studies by an unexpected toxicity. Work is currently in progress to improve the therapeutic index of the present class of nitroxyl lipids.     

Comparisons of EPR imaging and T1-weighted MRI for efficient imaging of nitroxyl contrast agents

The resolution and signal to noise ratio of EPR imaging and T(1)-weighted MRI were compared using an identical phantom. Several solutions of nitroxyl contrast agents with different EPR spectral shapes were tested. The feasibility of T(1)-weighted MRI to detect nitroxyl contrast agents was described. T(1)-weighted MRI can detect nitroxyl contrast agents with a complicated EPR spectrum easier and quicker; however, T(1)-weighted MRI has less quantitative ability especially for lipophilic nitroxyl contrast agents, because T(1)-relaxivity, i.e. accessibility to water, is affected by the hydrophilic/hydrophobic micro-environment of a nitroxyl contrast agent. The less quantitative ability of T(1)-weighted MRI may not be a disadvantage of redox imaging, which obtains reduction rate of a nitroxyl contrast. Therefore, T(1)-weighted MRI has a great advantage to check the pharmacokinetics of newly modified and/or designed nitroxyl contrast agents.     

Evaluation of diethylenetriaminepentaacetic acid-manganese(II) complexes modified by narrow molecular weight distribution of chitosan oligosaccharides as potential magnetic resonance imaging contrast agents

Novel conjugates of narrow molecular weight distribution of chitosan oligosaccharides (CSn; n=6, 8, 11) with manganese-diethylenetriaminepentaacetic acid (Mn-DTPA) as potential magnetic resonance imaging (MRI) contrast agents were synthesized. The structures were characterized by means of Fourier transform infrared spectra, ¹³C nuclear magnetic resonance, size exclusion chromatography and inductively coupled plasma atomic emission spectrometry. The characterization results showed that Mn-DTPA was successfully linked to aminated CSn by an amide function. The magnetic properties were characterized by in vitro and T₁-weighted FLASH image experiments. Relaxivities studies indicated that Mn-DTPA-CSn (n=8, 11) provided higher relaxivity, either in aqueous or bovine serum albumin solution (0.725 mM), than commercial contrast agent Gd-DTPA. The stability results showed that Mn-DTPA-CSn in aqueous were stable enough to prevent Mn^II ions from releasing. The preliminary in vitro and T₁-weighted FLASH image studies suggested that Mn-DTPA-CSn had the advantage of becoming promising MRI contrast agents.     

Dynamic nuclear polarization properties of nitroxyl radicals used in Overhauser-enhanced MRI for simultaneous molecular imaging

DNP parameters relevant to Overhauser-enhanced magnetic resonance imaging (OMRI) are reported for a few nitroxyl radicals and their corresponding (15)N and (2)H enriched analogues, used in simultaneous imaging by OMRI. DNP enhancement was measured at 14.529 mT, using a custom-built scanner operating in a field-cycled mode, for different concentrations, ESR irradiation times and RF power levels. DNP enhancements increased with agent concentration up to 2.5 mM and decreased above 3 mM, in tune with ESR line broadening measured at X-band as a function of the agent concentration. The proton spin-lattice relaxation times (T(1)) measured at very low Zeeman field (14.529 mT) and the longitudinal relaxivity parameters were estimated. The relaxivity parameters were in good agreement with those independently computed from the linear region of the concentration dependent enhancement. The leakage factor showed an asymptotic increase with increasing agent concentration. The coupling parameters of (14)N- and (15)N-labeled carbamoyl-PROXYL showed the interaction between the electron and nuclear spins to be mainly dipolar in origin. Upon (2)H labeling, about 70% and 40% increases in enhancement for (15)N- and (14)N-labeled nitroxyl agents were observed, respectively. It is envisaged that the results reported here may enable better understanding of the factors determining DNP enhancement to design suitable 'beacons' for simultaneous molecular imaging by OMRI.     

Comparison of T2 and LASER T2dagger image contrast in a rat model of acute cerebral ischemia

Previous studies have shown that T2(dagger)-weighted magnetic resonance images acquired using localization by adiabatic selective refocusing (LASER) can provide early tissue contrast following ischemia, possibly due to alterations in microscopic susceptibility within the tissue. The purpose of this study was to make a direct in vivo comparison of T2-, T2(dagger)- and diffusion-weighted image contrast during acute ischemia. Acute middle cerebral artery (MCA) occlusion was attempted in 14 rats using a modified Tamura approach incorporating electrocoagulation of the left MCA. T2(dagger)-weighted LASER images (Echo Time [TE]=108 ms), T2-weighted Carr-Purcell-Meiboom-Gill (CPMG) images (TE=110 ms) and diffusion-weighted images (b value=105 s/mm(2)) were acquired at 4 T within 1.5 h of ischemia onset. Tissue contrast in the MCA territory was quantified for histologically verified ischemic tissue (n=6) and in sham controls (n=4). T2(dagger)-weighted LASER images demonstrated greater contrast compared to the T2-weighted CPMG images, and more focal contrast compared to the diffusion-weighted images, suggesting different contrast mechanisms were involved.     

A simple way to acquire T(1)-weighted MR images of rat liver with respiratory triggering

To acquire high-resolution T(1)-weighted images of the liver in rats, for which breath-holding cannot be ensured, respiratory triggering is essential. At the respiratory rate of 30-60 times/min in rats, however, T(1)-weighted images cannot be obtained with simple triggering. As a simple solution to this, we applied multiple repeated acquisitions with one trigger signal. With this technique, sufficient T(1) contrast could be easily achieved in rat liver enhanced by gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid infusion.     

Depth and orientational dependencies of MRI T(2) and T(1ρ) sensitivities towards trypsin degradation and Gd-DTPA(2-) presence in articular cartilage at microscopic resolution

Depth and orientational dependencies of microscopic magnetic resonance imaging (MRI) T(2) and T(1ρ) sensitivities were studied in native and trypsin-degraded articular cartilage before and after being soaked in 1 mM Gd-DTPA(2-) solution. When the cartilage surface was perpendicular to B(0), a typical laminar appearance was visible in T(2)-weighted images but not in T(1ρ)-weighted images, especially when the spin-lock field was high (2 kHz). At the magic angle (55°) orientation, neither T(2)- nor T(1ρ)-weighted image had a laminar appearance. Trypsin degradation caused a depth- and orientational-dependent T(2) increase (4%-64%) and a more uniform T(1ρ) increase at a sufficiently high spin-lock field (55%-81%). The presence of the Gd ions caused both T(2) and T(1ρ) to decrease significantly in the degraded tissue (6%-38% and 44%-49%, respectively) but less notably in the native tissue (5%-10% and 16%-28%, respectively). A quantity Sensitivity was introduced that combined both the percentage change and the absolute change in the relaxation analysis. An MRI experimental protocol based on two T(1ρ) measurements (without and with the presence of the Gd ions) was proposed to be a new imaging marker for cartilage degradation.     

MRI with superparamagnetic iron oxide: efficacy in the detection and characterization of focal hepatic lesions

The purpose of this study was to evaluate the potential of superparamagnetic iron oxide particles (SPIO) as tissue specific contrast agent in magnetic resonance (MR) imaging in detection and characterization of focal hepatic lesions. We investigated 45 patients with focal hepatic lesions. T1-weighted SE (TR 650/TE 15 ms) and T2-weighted SE (TR 2015-2030/TE 45 and 90 ms) unenhanced images were obtained. After SPIO application we performed T1-weighted images with and T2-weighted images with and without fat suppression using the same image parameters. Liver signal intensity decreased by 74% (min 47%, max 83%) on T2-weighted images after application of the contrast agent. Benign lesions (FNH, adenoma) showed an average signal drop of 40% (min 20%, max 47%) whereas malignant lesions showed no significant change of signal intensity on post-contrast images. The mean tumor-to-liver contrast-to-noise ratio (C/N) was improved in all post-contrast sequences irrespective of the lesion type. An additional increase of tumor-to-liver contrast by use of fat suppression technique could be established in the slightly T2-weighted sequence (TE 45 ms). In metastases, divided in different size groups, we could determine a significant size relation of tumor-to-liver C/N. After SPIO application the number of detected lesions increased distinctly, especially small foci are more easily demonstrated. SPIO particles are a efficacious contrast agent for MR examinations of the liver. For tumor characterization T1- and T2-weighted pre- and post-contrast images are necessary. The T1-weighted sequences are helpful to differentiate benign lesions such as cysts and hemangiomas from malignant lesions. Detection and differential diagnoses of hepatic lesions are improved by use of the SPIO-particles.     

An albumin-based gold nanocomposites as potential dual mode CT/MRI contrast agent

In pursuit of the biological detection applications, recent years have witnessed the prosperity of novel multi-modal nanoprobes. In this study, biocompatible bovine serum albumin (BSA)-coated gold nanoparticles (Au NPs) containing Gd (III) as the contrast agent for both X-ray CT and T₁-weighted MR imaging is reported. Firstly, the Au NPs with BSA coating (Au@BSA) was prepared through a moderate one-pot reduction route in the presence of hydrazine hydrate as reducer. Sequentially, the BSA coating enables modification of diethylenetriaminepentaacetic acid (DTPA) as well as targeting reagent hyaluronic acid (HA), and further chelation of Gd (III) ions led to the formation of biomimetic nanoagent HA-targeted Gd-Au NPs (HA-targeted Au@BSA-Gd-DTPA). Several techniques were used to thoroughly characterize the formed HA-targeted Gd-Au NPs. As expected, the as-prepared nanoagent with mean diameter of 13.82 nm exhibits not only good colloid stablility and water dispersibility, but also satisfying low cytotoxicity and hemocompatibility in the tested concentration range. Additionally, for the CT phantoms, the obtained nanocomplex shows an improved contrast in CT scanning than that of Au@BSA as well as small molecule iodine-based CT contrast agents such as iopromide. Meanwhile, for the T₁-weighted MRI images, there is a linear increase of contrast with concentration of Gd for the two cases of HA-targeted Gd-Au NPs and Magnevist. Strikingly, the nanoagent we explored displays a relatively higher r₁ relaxivity than that of commercial MR contrast agents. Therefore, this newly constructed nanoagent could be used as contrast agents for synergistically enhanced X-ray CT and MR phantoms, holding promising potential for future biomedical applications.     

Recurrent hepatocellular carcinoma versus radiation-induced hepatic injury: differential diagnosis with MR imaging

The objective of this study was to assess the value of MR imaging in the differentiation between a recurrent hepatocellular carcinoma (HCC) and a radiation-induced hepatic injury. Nine male patients with suspected recurrence after radiotherapy for HCC underwent T(2)-, T(1)-weighted imaging and Gd-DTPA enhanced dynamic studies. T(2) relaxation times, signal intensity ratios in T(1)-weighted images (WI) and the relative enhancement of the dynamic study were calculated. Recurrent tumors and the irradiated area showed similar image characteristics: hypointense in T(1)-WI and hyperintense in T(2)-WI. T(2) values and signal intensity ratios in the T(1)-WI were not significantly different. In the gadolinium-enhanced dynamic study, a recurrent HCC showed early enhancement, followed by a rapid washout. However, the irradiated liver parenchyma showed hyperintensity from an early phase, and contrast enhancement tended to be more prominent and prolonged at the end of the dynamic studies. The characteristic findings of the dynamic MR study enable us to distinguish between a recurrent HCC and a radiation-induced hepatic injury.     

Structure activity relationship of magnetic particles as MR contrast agents

Structure activity relationship (SAR) of superparamagnetic MR contrast agents is discussed based on physicochemical properties and relaxivity data of 16 different particles. All the magnetic particles reduce both relaxation times, T1 and T2. The effect on T2 is stronger than the effect on T1. The relaxation efficacy varies over a wide range. Minor modifications in the preparation of the magnetic particles result in products with different susceptibility properties. The T2 relaxivity is dependent upon the magnetic susceptibility as well as particle size. Small particles reduce the relaxation times to a larger extent than the larger particles. No significant difference in relaxivity is observed between compact and porous particles. Magnetic particles coated with nonmagnet polymer are effective relaxation agents, while nonmagnetic monodisperse particles show no effect on the relaxivity.     

MR imaging of the her2/neu and 9.2.27 tumor antigens using immunospecific contrast agents

Molecular imaging of tumor antigens using immunospecific magnetic resonance (MR) contrast agents is a rapidly evolving field, which can potentially aid in early disease detection, monitoring of treatment efficacy, and drug development. In this study, we designed, synthetized, and tested in vitro two novel monocrystalline iron oxide nanoparticles (MION) conjugated to antibodies against the her2/neu tyrosine kinase receptor and the 9.2.27 proteoglycane sulfate. MION was synthetized by coprecipitation of iron II and iron III salts in 12-kD dextran solution; antibody coupling was performed by reductive amination. The relaxivity of the conjugates was 24.1-29.1 mM(-1) s(-1), with 1.8 to 2.1 antibody molecules per nanoparticle. A panel of cultured melanoma and mammary cell lines was used for testing. The cells were incubated with the particles at 16-32 microg Fe/ml in culture medium for 3 h at 37 degrees C, and investigated with immune fluorescence, transmission electron microscopy (TEM), MRI of cell suspensions in gelatine, and spectrophotometric iron determination. All receptor-positive cell lines, but not the controls, showed receptor-specific immune fluorescence, and strong changes in T(2) signal intensity at 1.5 T. The changes in 1/T(2) were between 1.5 and 4.6 s(-1) and correlated with the amount of cell-bound iron (R = 0.92). The relaxivity of cell-bound MION increased to 55.9 +/- 10.4 mM(-1) s(-1). TEM showed anti-9.2.27 conjugates binding to the plasma membrane, while the anti-her2/neu conjugates underwent receptor-mediated endocytosis. In conclusion, we obtained receptor-specific T(2) MR contrast with novel covalently bound, multivalent MION conjugates with anti-9.2.27 and anti-her2/neu to image tumor surface antigens. This concept can potentially be expanded to a large number of targets and to in vivo applications.     

Magnetic resonance T1ρ imaging of osteoarthritis: a rabbit ACL transection model

Objective

The objective of this study was to develop quantitative T_1ρ-weighted magnetic resonance imaging methodology for the detection and characterization of cartilage degeneration in a rabbit anterior cruciate ligament (ACL) transection model.

Methods

The right knee ACLs of 18 adult female New Zealand white rabbits were transected. The left knee joint served as a sham control. The rabbits were euthanized at 3 (Group 1), 6 (Group 2) and 12 (Group 3) weeks postoperatively. High-resolution 3D fat-saturated spoiled gradient echo images and T_1ρ-weighted images were obtained in both the sagittal and axial planes at 3 T using a quadrature wrist coil. Following MR analysis, histological slides from the lateral femoral condyle cartilage were graded using the Mankin grading system.

Results

For all three groups, the average overall T_1ρ values were significantly higher in the ACL-transected knee compared to control knee, and the percentage differences in T_1ρ values between ACL-transected and control increased with the duration of time after transection. The average Mankin score for ACL-transected knees was higher than that for control for each time point, but this difference was statistically significant only for all groups combined.

Conclusions

This study demonstrates the feasibility of using T_1ρ-weighted imaging as a useful tool in the detection and quantification of cartilage damage in all knee compartments in an ACL-transected rabbit model of cartilage degeneration.     

Magnetic resonance image enhancement using stochastic resonance in Fourier domain

Objective

In general, low-field MRI scanners such as the 0.5- and 1-T ones produce images that are poor in quality. The motivation of this study was to lessen the noise and enhance the signal such that the image quality is improved. Here, we propose a new approach using stochastic resonance (SR)-based transform in Fourier space for the enhancement of magnetic resonance images of brain lesions, by utilizing an optimized level of Gaussian fluctuation that maximizes signal-to-noise ratio (SNR).

Materials and Methods

We acquired the T1-weighted MR image of the brain in DICOM format. We processed the original MR image using the proposed SR procedure. We then tested our approach on about 60 patients of different age groups with different lesions, such as arteriovenous malformation, benign lesion and malignant tumor, and illustrated the image enhancement by using just-noticeable difference visually as well as by utilizing the relative enhancement factor quantitatively.

Results

Our method can restore the original image from noisy image and optimally enhance the edges or boundaries of the tissues, clarify indistinct structural brain lesions without producing ringing artifacts, as well as delineate the edematous area, active tumor zone, lesion heterogeneity or morphology, and vascular abnormality. The proposed technique improves the enhancement factor better than the conventional techniques like the Wiener- and wavelet-based procedures.

Conclusions

The proposed method can readily enhance the image fusing a unique constructive interaction of noise and signal, and enables improved diagnosis over conventional methods. The approach well illustrates the novel potential of using a small amount of Gaussian noise to improve the image quality.     

MRI characterization of residual mediastinal masses in Hodgkin's disease: long-term follow-up

Our purpose was to evaluate the role of MRI in distinguishing fibrous from active residual masses in treated Hodgkin's disease. Forty patients with residual mediastinal mass larger than 1.5 cm underwent MRI 1, 3, 6, and 12 months after the end of cycles of prescribed chemotherapy or combined chemoradiotherapy. The MRI examinations were performed on a 0.5 and a 1.5 T systems, using T(1) before and after gadolinium injection and T(2)-weighted sequences. Each time the residual mass was evaluated in size and signal intensity on spin echo (SE) T(2)-weighted images and on SE T(1)-weighted images after contrast medium. Low signal intensity and low contrast enhancement were considered signs of inactive residues; homogeneous high signal intensity and high contrast enhancement were indicative of active residual disease; heterogeneous signal intensity and heterogeneous contrast enhancement were indicative of partial remission or necrotic/inflammatory phenomena. MR showed high diagnostic accuracy in the evaluation of Hodgkin's mediastinal residues after treatment, if performed at least 6 months after the end of therapy, reaching the highest sensitivity and specificity values at 12 month follow-up (considering the three parameters-T(2) signal intensity, contrast-enhancement, and size-all together). If we consider the single parameters individually, we can observe that size variation remains the more valuable parameter to predict or to exclude a relapse. MR diagnostic accuracy at the 6-month follow-up was lower due to the higher incidence of inhomogeneous pattern. The accuracy of MR performed at 1 and at 3 months after the end of therapy was not satisfying. This represents a clinical problem because the most important clinical decisions have to be taken just in this early post-treatment phase.     

Euterpe Olerácea (Açaí) as an alternative oral contrast agent in MRI of the gastrointestinal system: preliminary results

Using contrast agents is a common practice in medical imaging protocols. Paramagnetic properties of certain compounds present in contrast agents can affect magnetic resonance imaging (MRI) signals. For abdominal applications, they are usually injected, but may also be administered orally. However, their use as a routine technique is limited, mainly due to the lack of appropriate oral contrast agents. We herein present the preliminary characterization and results for implementation of Euterpe Olerácea (popularly named A?aí) as a possible clinical oral contrast agent for MRI of the gastrointestinal tract. The pulp of A?aí, a fruit from the Amazon area, presented an increase in T(1)-weighted MRI signal, equivalent to that of gadolinium-diethyltriamine pentaacetic acid, and a decrease in T(2)-weighted images. We looked for intrinsic properties that could be responsible for the T(1) signal enhancement and T(2) opacification. Atomic absorption spectra revealed the presence of Fe, Mn and Cu ions in A?ai. The presence of such ions contribute to the susceptometric value found of chi = -4.83 x 10(-6). This finding assents with the hypothesis that image contrast changes were due to the presence of paramagnetic material. The first measurements in vivo demonstrate a clear increase of contrast, in T(1)-weighted images, due to the presence of A?aí. Consistently, the opacification in a T(2)-weighted acquisition was evident, revealing a good contrast on bowel walls of gastric tissues.     

MR imaging findings of infectious cholangitis

The purpose of this study was to evaluate the appearance of infectious cholangitis on MRI. The MR images of 13 patients (9 women, 4 men; age range, 14-79 years) with clinically confirmed infectious cholangitis, who represent our complete 9.5 year experience with this entity, were retrospectively evaluated. All MR studies were performed at 1.5 T and included: in-phase and out-of-phase T(1)-weighted spoiled gradient echo (SGE), T(2)-weighted fat-suppressed echo train spin echo, single shot T(2)-weighted sequences, and serial postgadolinium T(1)-weighted SGE sequences without and with fat-suppression. The biliary ductal system was evaluated regarding presence of dilatation, stenosis, wall irregularities, wall thickening, and gadolinium enhancement of duct walls. The liver parenchyma was evaluated regarding focal signal abnormalities on precontrast and serial postgadolinium images. Biliary ductal dilatation was observed in 100% of patients. Mild to moderate thickening of bile duct walls combined with increased enhancement on postgadolinium images was observed in 92% of patients. The liver parenchyma showed periportal or wedge-shaped areas of hyperintense signal on T(2)-weighted images in 69% of patients. On T(1)-weighted images, 54% of patients showed areas of hypointense signal and 15% of patients showed wedge-shaped hyperintense areas. Areas with increased enhancement on immediate postgadolinium SGE were observed in 58% of patients, and in 42% of patients increased enhancement persisted on 2 min postgadolinium fat-suppressed images. Distinctive MRI findings on pre- and postgadolinium images are appreciated for infectious cholangitis.     

Dynamic contrast-enhanced MRI of Implanted VX2 tumors in rabbit muscle: comparison of Gd-DTPA and NMS60

We studied the dynamics of injected contrast enhancement in implanted VX2 tumors in rabbit thigh muscle. We compared two contrast agents Gd-DTPA and NMS60, a novel gadolinium containing trimer of molecular weight 2.1 kd. T1-weighted spin echo images were acquired preinjection and at 5-60 min after i.v. injection of 0.1 mmol/kg of agent. Dynamic T1-weighted SPGR images (1.9 s/image) were acquired during the bolus injection. Male NZW rabbits (n = 13) were implanted with approximately 2 x 10(6) VX2 tumor cells and grew tumors of 28+/-27 mL over 12 to 21 days. NMS60 showed significantly greater peak enhancement in muscle, tumor rim, and core compared to DTPA in both T1-weighted and SPGR images. NMS60 also showed delayed peak enhancement in the dynamic scans (compared to Gd-DTPA) and significantly reduced leakage rate constant into the extravascular space for tumor rim (K21 = 5.1 min(-1) vs. 11.5 min(-1) based on a 2 compartment kinetic model). The intermediate weight contrast agent NMS60 offers greater tumor enhancement than Gd-DTPA and may offer improved regional differentiation on the basis of vascular permeability in tumors.     

Improved T(1)-weighted dynamic contrast-enhanced MRI to probe microvascularity and heterogeneity of human glioma

Dynamic contrast-enhanced (DCE) T(1)-weighted magnetic resonance imaging (MRI) is a powerful tool capable of providing quantitative assessment of contrast uptake and characterization of microvascular structure in human gliomas. The kinetics of the bolus injection doped with increasing concentrations of gadopentate dimeglumine (Gd-DTPA) depends on tissue as well as pulse sequence parameters. A simple method is described that overcomes the limitation of relative signal increase measurement and may lead to improved accuracy in quantification of perfusion indices of glioma. Based on an analysis of the contrast behavior of spoiled gradient-recalled echo sequence; a parameter K with arbitrary unit 5.0 is introduced, which provides a better approximation to the differential T(1) relaxation rate. DCE-MRI measurements of relative cerebral blood volume (rCBV) and cerebral blood flow (rCBF) were calculated in 25 patients with brain tumors (15=high-grade glioma, 10=low-grade glioma). The mean rCBV was 6.46 +/- 2.45 in high-grade glioma and 2.89 +/- 1.47 in the low-grade glioma. The rCBF was 3.94 +/- 1.47 in high-grade glioma while 2.25 +/- 0.87 in low-grade glioma. A significant difference in rCBF and rCBV was found between high- and low-grade gliomas. This simple and robust technique reveals the complexity of tumor vasculature and heterogeneity that may aid in therapeutic management especially in nonenhancing high-grade gliomas. We conclude that the precontrast medium steady-state residue parameter K may be useful in improved quantification of perfusion indices in human glioma using T(1)-weighted DCE-MRI.     

Equilibrium signal intensity mapping, an MRI method for fast mapping of longitudinal relaxation rates and for image enhancement

INTRODUCTION: Inhomogeneity of magnetic fields, both B(0) and B(1), has been a major challenge in magnetic resonance imaging (MRI). Field inhomogeneity leads to image artifacts and unreliability of signal intensity (SI) measurements. This work proposes and shows the feasibility of generating equilibrium signal intensity (SI(Eq)) maps that can be utilized either to speed up relaxation-rate measurement or to enhance image quality and relaxation-rate-based weighting in various applications. METHODS: A 1.5-T MRI scanner was used. In canines (n=4), myocardial infarction was induced, and 48 h after the administration of 0.05 mmol kg(-1) Gd(ABE-DTTA), a contrast agent with slow tissue kinetics, in vivo R(1) mapping was carried out using an inversion recovery (IR)-prepared, fast gradient-echo sequence with varying inversion times (TIs). To test the SI(Eq) mapping method without the confounding effects of motion and blood flow, we carried out ex vivo R(1) mapping after the administration of 0.2 mmol kg(-1) Gd(DTPA) using an IR-prepared, fast spin-echo sequence in another group of dogs (n=2). R(1,full) maps and SI(Eq) maps were generated from the data from both sequences by three-parameter nonlinear curve fitting of the SI versus TI dependence. R(1,full) maps served as the reference standard. Raw IR images were then divided by the SI(Eq) maps, yielding corrected SI maps (COSIMs). Additionally, R(1) values were calculated from each single-TI image separately, using the SI(Eq) value and a one-parameter curve-fitting procedure (R(1,single)). Voxelwise correlation analysis was carried out for the COSIMs and the R(1,single) maps, both versus the standard R(1,full) maps. Deviations of R(1,single) from R(1,full) were statistically evaluated. RESULTS: In vivo, COSIM versus R(1,full) showed significantly (P<.05) better correlation [correlation coefficient (CC)=0.95] than SI versus R(1,full) with a TI=700-800 ms, which is 200-300 ms longer than the tau(null) (500 ms) of viable myocardium. With such TIs, SI versus R(1,full) yielded CCs of 0.86-0.88. R(1,single) versus R(1,full) yielded a peak CC of 0.96 at TI=700-900 ms. Mean deviations of R(1,single) from R(1,full) were below 5% for TIs between 500 and 1000 ms. Ex vivo, where tau(null) was 300 ms, the advantage of correction with SI(Eq) was not in the improvement of linear correlation but more in the reduction of scatter. Peak CCs for SI versus R(1,full) and COSIM versus R(1,full) at TI=500 ms were 0.96 for both. The ex vivo CC for R(1,single) versus R(1,full) at TI=500 ms was 0.98. Mean deviations of R(1,single) from R(1,full) were below 5% for TIs between 400 and 700 ms. CONCLUSIONS: Once the corresponding SI(Eq) map is obtained from a control stack, R(1) can be obtained accurately, using only a single IR image and without the need for a stack of TI-varied images. This approach could be applied in various dynamic MRI studies where short measurement time, once the dynamics has started, is of essence. When using this method with IR-prepared T(1)-weighted images, it is essential that the single TI be chosen such that the longitudinal relaxation in all voxels of interest would have passed tau(null). SI(Eq) maps are also useful in eliminating confounders from MR images to allow obtaining SI values that reflect more faithfully the relaxation parameter (R(1)) sought.