The measurement of extracellular water volumes in tissues by gadolinium modification of 1H-NMR spin lattice (T1) relaxation

The present studies were conducted in RIF-1, M5076 and Panc02 murine tumor models to compare extracellular water measurements made by 51Cr-EDTA dilution techniques and a new method which exploits the concentration dependent modification of 1H-NMR proton relaxation by Gadolinium-DTPA-dimethyl glucamine (Gd-DTPA-dimeg) in plasma and tissues. The time dependent changes in T1 modification in tissue and plasma were determined at various intervals after i.v. injection of 0.1 ml of 100 mM Gd-DTPA-dimeg and Gd concentrations determined from standard curves of Gd concentration dependent T1 modification of mouse plasma. Comparison of tissue and plasma Gd concentrations permitted the calculation of Gd-DTPA-dimeg distribution volumes. In unperturbed RIF-1, M5076 and Panc02 tumors, Gd-DTPA-dimeg distribution volumes determined by the T1 modification technique were similar to extracellular water spaces determined by 51Cr-EDTA dilution assays. In mouse liver, the 51Cr-EDTA assay resulted in artifactually high extracellular water space estimates due to internalization of the probe; Gd-DTPA-dimeg distribution volumes determined in liver with both the 153Gd-DTPA-dimeg and by the T1 modification method were approximately 150 ul/gram. The Gd-DTPA-dimeg T1 modification method also provided good approximations of changes in extracellular water volumes in RIF-1 tumors after dexamethasone and cyclophosphamide treatments. These results indicate that Gd-DTPA-dimeg modification of proton relaxation may be extremely useful for monitoring changes in tumor water dynamics during cancer therapy.     

Evaluation of CH3-DTPA-Gd (NMS60) as a new MR contrast agent: early phase II study in brain tumors and dual dynamic contrast-enhanced imaging

PURPOSE: A newly developed contrast material, CH3-DTPA-Gd (NMS60), a trimer containing 3 Gd(3+) atoms per molecule, has been shown to offer greater enhancement and longer vascular retention than gadopentetate dimeglumine (Gd-DTPA) in animals. We report on our early phase II study on NMS60 in brain tumor patients together with supplementary investigations. METHODS AND MATERIALS: The longitudinal relaxation rate (R(1)=1/T(1)) and the transverse relaxation rate (R(2)*=1/T(2)*) of NMS60 and Gd-DTPA were determined at 20 degrees C in water at 1.5 T. An NMS60 dose of 0.1 or 0.2 mmol (Gd)/kg was randomly assigned and administered to 10 patients (five women, five men; mean age: 49 years) with brain tumors. Safety and contrast-enhancing ability of NMS60 were evaluated. Dual dynamic contrast-enhanced T(1) and R(2)* studies (DUCE imaging) were also carried out in two patients. RESULTS: Regarding the relaxivity per Gd, R(1) and R(2)* of NMS60 were 9.5 and 11.0 (mmol/L x s)(-1), respectively, compared to 4.8 and 7.2 (mmol/L x s)(-1) for Gd-DTPA. Although a transient slight increase of alanine aminotransferase was observed in one case, no other adverse reactions were observed after administration of NMS60. Contrast enhancement by NMS60 was excellent at both concentrations, and when tumor detectability was assessed with a five-point scale, the diagnostic usefulness was 4 or higher in all cases. In DUCE imaging, NMS60 appeared to show high signal intensity, when compared with the data obtained separately for Gd-DTPA. CONCLUSION: NMS60 had a high contrasting effect and little toxicity, and is expected to be clinically useful.     

The gadolinium complexes with polyoxometalates as potential MRI contrast agents

The two gadolinium (Gd) polyoxometalates, K(15)[Gd(BW(11)O(39))(2)] [Gd(BW(11))(2)] and K(17)[Gd(CuW(11)O(39))(2)] [Gd(CuW(11))(2)] have been evaluated by in vivo and in vitro experiments as the candidates of potential tissue-specific magnetic resonance imaging (MRI) contrast agents. T(1) relaxivities of 17.12 mM(-1) x s(-1) for Gd(BW(11))(2) and 19.95 mM(-1) x s(-1) for Gd(CuW(11))(2) (400 MHz, 25 degrees C) were much higher than that of the commercial MRI contrast agent (GdDTPA). Their relaxivities in bovine serum albumin and human serum transferrin solutions were also reported. After administration of Gd(BW(11))(2) and Gd(CuW(11))(2) to Wistar rats, MRI showed longer and remarkable enhancement in rat liver and favorable renal excretion capability. The signal intensity increased by 37.63+/-3.45% for the liver during the whole imaging period (100 min) and by 61.47+/-10.03% for kidney within 5-40 min after injection at 40+/-1-micromol x kg(-1) dose for Gd(CuW(11))(2), and Gd(BW(11))(2) induced 50.44+/-3.51% enhancement in the liver in 5-50-min range and 61.47+/-10.03% enhancement for kidney within 5-40 min after injection at 39+/-4 micromol x kg(-1) dose. In vitro and in vivo study showed that Gd(BW(11))(2) and Gd(CuW(11))(2) are favorable candidates as tissue-specific contrast agents for MRI.     

A comparison of the sensitivity of MRI after double- and triple-dose Gd-DTPA for detecting enhancing lesions in multiple sclerosis

We compared the number and volume of enhancing lesions detected in patients with multiple sclerosis (MS) seen on post-contrast T(1)-weighted scans obtained after the injection of different gadolinium-DTPA (Gd) doses. Enhanced magnetic resonance imaging (MRI) scans were obtained from 16 patients with relapsing remitting or secondary progressive MS on two different occasions separated by an interval of approximately 24 h. On the first occasion, enhanced scans were obtained 15 min after the injection of a double dose of Gd (0.2 mmol/Kg), on the second 15 min after the injection of a triple dose (0.3 mmol/Kg) of Gd. Scans were assessed by consensus in a random order by two observers unaware of the dose of Gd used. We counted the same 30 enhancing lesions on both double dose and triple dose scans from 9 patients. The mean (SD) volumes of enhancing lesions were 1.7 (2.7) mL on double dose and 1.9 (3.4) mL on triple-dose scans. This difference was not statistically significant. This study demonstrated that double dose of Gd has a sensitivity for detecting MS activity similar to that of a triple dose, with the advantage of a significant cost saving.     

Effects of the operating magnetic field on potential NMR contrast agents

Paramagnetic metal ions have shown promise as contrast agents for nuclear magnetic resonance (NMR) imaging. Their ability depends upon modification of the relaxation times (T1 and T2) through dipolar interactions. These interactions cause the effectiveness of the agents to be sensitive to the operating magnetic field. Studies are presented of the operating field dependence (frequency dispersion) of two metal-chelate complexes, Gd+3-ethylenediaminetetraacetate (EDTA) and Mn+2-EDTA, in a physiologically balanced electrolyte solution. Inversion recovery experiments were performed on two concentrations of each metal-chelate complex at five resonant frequencies. The frequency dispersion curves were similar in appearance for those of the corresponding aqueous solutions. The Mn+2 complex showed no unusual concentration effects. The Gd+3 complex showed an unexpected concentration dependence in the dispersion behavior. This is attributed to a difference in the dipolar correlation time between the two solutions. With its unique correlation time in electrolyte solutions, predictions of relaxation rate changes in studies in vivo may be easier for the Mn+2-EDTA complex.     

Gadolinium oxide: a protoype agent for contrast enhanced imaging of the liver and spleen with magnetic resonance

Gd2O3 particles (less than 2 microns) in suspension were evaluated as a potential contrast agent for liver-spleen imaging with magnetic resonance. The agent was administered IV to rabbits in doses ranging from 10 to 120 mumol/kg and the tissues removed after sacrifice for in vitro T1 and T2 analysis. The temporal response was determined in liver and spleen samples of rabbits given a fixed dose (60 mumol/kg) and sacrificed at intervals from 15 min to 60 hr later. Documentation of the subanatomic location of Gd2O3 particles in tissue was accomplished by electron microscopy and x-ray dispersion microanalysis. T1 weighted images were obtained at 0.12T on a prototype resistive scanner. The liver, spleen, and lung relaxation times are very responsive to Gd2O3 IV and the effect is dose related. A peak effect is observed between 3-7 hr after injection and relaxation times may normalize by 60 hr. By electron microscopic and x-ray analysis, Gd2O3 is most prominently found in the hepatic and splenic sinusoids. The images show marked enhancement of liver and splenic tissues, aiding in the clear delineation of these tissues from neighboring structures.     

Prognosticating brain tumor patient survival after laser thermotherapy: Comparison between neuroradiological reading and semi-quantitative analysis of MRI data

Background and purposeGiven increasing interest in laser interstitial thermotherapy (LITT) to treat brain tumor patients, we explored if examining multiple MRI contrasts per brain tumor patient undergoing surgery can impact predictive accuracy of survival post-LITT.Materials and methodsMRI contrasts included fluid-attenuated inversion recovery (FLAIR), T1 pre-gadolinium (T1pre), T1 post-gadolinium (T1Gd), T2, diffusion-weighted imaging (DWI), apparent diffusion coefficient (ADC), susceptibility weighted images (SWI), and magnetization-prepared rapid gradient-echo (MPRAGE). The latter was used for MRI data registration across preoperative to postoperative scans. Two ROIs were identified by thresholding preoperative FLAIR (large ROI) and T1Gd (small ROI) images. For each MRI contrast, a numerical score was assigned based on changing image intensity of both ROIs (vs. a normal ROI) from preoperative to postoperative stages. The fully-quantitative method was based on changing image intensity across scans at different stages without any human intervention, whereas the semi-quantitative method was based on subjective criteria of cumulative trends across scans at different stages. A fully-quantitative/semi-quantitative score per patient was obtained by averaging scores for each MRI contrast. A standard neuroradiological reading score per patient was obtained from radiological interpretation of MRI data. Scores from all 3 methods per patient were compared against patient survival, and re-examined for comorbidity and pathology effects.ResultsPatient survival correlated best with semi-quantitative scores obtained from T1Gd, ADC, and T2 data, and these correlations improved when biopsy and comorbidity were included.ConclusionThese results suggest interfacing neuroradiological readings with semi-quantitative image analysis can improve predictive accuracy of patient survival.     

Evaluation of two new gadolinium chelates as contrast agents for MRI

Two new gadolinium chelates were investigated for potential use as tissue-specific contrast agents for magnetic resonance imaging. In vitro measurements of stability constants, octanol/water partition coefficients and relaxation times in solutions of water and human serum albumin (HSA) were performed with each new chelate and compared with gadolinium-diethylenetriamine pentaacetic acid, Gd(DTPA). Biodistribution studies and magnetic resonance imaging in rats were used to evaluate the new chelates in vivo. The stability constants (log K) of gadolinium-N,N″-bis(3-hydroxy-6-methyl-2-pyridylmethyl)diethylenetriamine-N,N′,N″-triacetic acid, Gd(DTTA-HP), and gadolinium-1,7-13-triaza-4,10-16-trioxacyclooctadecane-N,N′,N″-triacetic acid, Gd(TTCT), were determined to be 23.65 and 18.07, respectively. These can be compared to a literature value of 22.46 for Gd(DTPA). Octanol/water partition coefficients for both complexes showed they were more lipophilic than Gd(DTPA). Gd(DTTA-HP) exhibited a smaller relaxivity in water but a larger relaxivity in 4% HSA than Gd(DTPA). Gd(TTCT) exhibited a lower relaxivity than Gd(DTPA) in both water and 4% HSA. Both complexes showed similar biodistributions to Gd(DTPA) no carrier-added concentrations. Gd(DTTA-HP) had a greater percent change in signal intensity than Gd(DTPA) on T₁-weighted spin-echo images in the heart, liver, and kidney. Percent change in signal intensity for Gd(TTCT) was lower than Gd(DTPA) in heart, liver, and kidney.     

The effect of dexamethasone on tissue water distribution and proton relaxation in Panc02 tumors

The present experiments were conducted to determine the effects of dexamethasone mediated changes in tumor water distribution on proton relaxation times (T1, T2) in a murine pancreatic adenocarcinoma (Panc02). Spin lattice (T1) and spin-spin (T2) relaxation times were determined by ex vivo methods (10MHz) and by in vivo imaging techniques (6.25 MHz) at various intervals after single or multiple dexamethasone treatments. In complementary studies, dexamethasone mediated changes in tumor capillary permeability, tumor water distribution, relative tumor blood flow and tumor cell proliferation were also determined.

Proton spin lattice (T1) and spin-spin (T2 relaxation times for Panc02 tumors shortened within two hours of a single dexamethasone treatment. The time course and magnitude of this response was dexamethasone dose dependent. The time dependent changes in T1 and T2 after dexamethasone were similar at 10 MHz (ex vivo) and 6.25 MHz (in vivo imaging). Although dexamethasone produced little or no change in total tumor water content and tumor cell proliferation, transient changes in the physiologic distribution of tumor water were clearly demonstrated.

The data supports the idea that dexamethasone induced changes in the distribution of tumor water were mediated by changes in capillary permeability and tumor blood flow. These physiologic responses produced serial changes in tumor extracellular extravascular water content that were consistent with the observed changes in tumor T1 and T2. The results from these experiments might imply that therapy associated changes in tumor proton relaxation times may not only reflect changes in tissue water content, but may also reflect physiologic responses which alter the distribution of tissue water and solute.     

Determination of the effective correlation time modulating 1H NMR relaxation processes of bound water in protein solutions

The relaxation in protein solutions has mainly been studied by nuclear magnetic relaxation dispersion (NMRD) techniques. NMRD data have mostly been analyzed in terms of fast chemical exchange of water between free water and water bound to proteins. Several approaches were used for the estimation of correlation time modulating the relaxation mechanism of bound water. On the other hand, in a nuclear magnetic resonance experiment, the relaxation rates of protein solutions (1/T1 and 1/T2) and also those of free water (1/T1f and 1/T2f) are measurable. However, the relaxation rates of bound water (1/T1b and 1/T2b) are not. Despite this, equating (1/T1-1/T1f)/2(1/T2-1/T2f) to (1/T1b)/2(1/T2b) leads to an expression involving only an effective tau that is related to the rotational correlation time (tau r) of proteins. Equating the ratios may therefore give a simple alternative method for the determination of tau r even if this method is limited to a single resonance frequency. In this work, a formula was derived for the solution of the effective tau. Then, the 1/T1 and 1/T2 in solutions of two globular proteins (lysozyme and albumin) and one nonglobular protein (gamma-globulin) were measured for different amounts of each protein. Next, the values of 1/T1 and 1/T2 were plotted vs. protein concentrations, and then the slopes of the fits were used in the derived equation for determining the effective tau values. Finally, the rotational correlation time tau r, calculated from tau, was used in the Stokes-Einstein relation to reproduce relevant radii. The effective tau values of lysozyme, albumin and gamma-globulin were found to be 5.89 ns, 7.03 ns and 8.8 ns, respectively. tau r values of albumin and lysozyme produce their Stokes radii. The present data suggest that use of the measurable ratio in the derived formula may give a simple way for the determination of the correlation times of lysozyme and albumin.     

MRI characterization of 9L-glioma in rat brain at 4.7 Tesla

In vivo estimation of intracranial tumor progression is important in tumor treatment response studies in animal models. High resolution MR images at 4.7 T of 9L-gliomas stereotactically implanted in Fisher-344 rat brains were obtained. Due to elongation of T1 at higher fields, tissue contrast is diminished in T1-weighted images. However, normal anatomy and vasogenic edema are clearly discerned in T2-weighted images (echo times of greater than 50 ms and recycle times of greater than 2 sec). Tumor tissue is not always clearly delineated. Images obtained after administration of contrast agents (Gadolinium DTPA), with short TR (0.6 sec) selectively enhanced the tumorous tissue, with little effect upon normal tissue and edema. Good correlation of enhanced tumor lesions has been observed with histological examination of formalin fixed brains. Relaxation times (T1 and T2) of tumor and normal tissues were measured using stimulated-echo and multi-echo sequences, respectively. Serial images corresponding to tumor growth were recorded, from which tumor volume progression was monitored.     

Temperature dependence of proton relaxation times in vitro

Accurate measurement of tissue relaxation characteristics is dependent on many factors, including field strength and temperature. The purpose of this study was to evaluate the relationship between sample temperature, viscosity and proton spin-lattice relaxation time (T1) and spin-spin relaxation time (T2). A review of two basic models of relaxation the simple molecular motion model and the fast exchange two state model is given with reference to their thermal dependencies. The temperature dependence for both T1 and T2 was studied on a 0.15 Tesla whole body magnetic resonance imager. Thirteen samples comprising both simple and complex materials were investigated by using a standard spin-echo (SE) technique and a modified Carr-Purcell-Meiboom-Gill (CPMG) multi-echo sequence. A simple linear relationship between T1 and temperature was observed for all samples over the range of 20 degrees C to 50 degrees C. There is an inverse relationship between viscosity and T1 and T2. A quantity called the temperature dependence coefficient (TDC) is introduced and defined as the percent rate of change of the proton relaxation time referenced to a specific temperature. The large TDC found for T1 values, e.g. 2.37%/degrees C for CuSO4 solutions and 3.59%/degrees C for light vegetable oils at 22 degrees C, indicates that a temperature correction should be made when comparing in-vivo and in-vitro T1 times. The T2 temperature dependence is relatively small.     

Water phases in rat striated muscles as determined by T2 proton NMR relaxation times

The spin echo decay curve of NMR protons in in-vitro rat muscle is two or three exponential as Hazlewood demonstrated in 1974. This author hypothesized that the longer T2 component is extracellular water and that the medium T2 is intracellular water. Our purpose was to test the histological significance of these two T2. Variations of water contents in two types of rat muscles were induced by electrical stimulation and osmotic diuresis and their incidence on the decomposition of the proton spin echo signal analysed. Decomposition of signal in resting muscles revealed two phases with T2 values similar to the Hazlewood's: a short phase, S, with T2 of 40 ms (20 MHz, 276 degrees K) representing 90-97% of the total signal and a long one, L, with T2 of 100-120 ms representing 3-10% of the signal. Increasing vascular volume appeared to increase the percentage of phase (L) in the total signal. Osmotic diuresis decreased the volume of the phase (S) and increased the volume of the phase (L). The use of Gd-DTPA allowed to differentiate the vascular compartment: Gd DTPA decreased in a great extent the T2 values of phase (L) and in low extent the T2 values of phases (S). From these results, it appears that phase (L) could correspond to vascular volume and that phase (S) would be interstitial and intracellular water. Elements of comparison with classical methods for determination of water compartmentation in tissues are given.     

Electron spin relaxation of triarylmethyl radicals in fluid solution

Electron spin relaxation times of a Nycomed triarylmethyl radical (sym-trityl) in water, 1:1 water:glycerol, and 1:9 water:glycerol were measured at L-band, S-band, and X-band by pulsed EPR methods. In H(2)O solution, T(1) is 17+/-1 micros at X-band at ambient temperature, is nearly independent of microwave frequency, and exhibits little dependence on viscosity. The temperature dependence of T(1) in 1:1 water:glycerol is characteristic of domination by a Raman process between 20 and 80 K. The increased spin-lattice relaxation rates at higher temperatures, including room temperature, are attributed to a local vibrational mode that modulates spin-orbit coupling. In H(2)O solution, T(2) is 11+/-1 micros at X-band, increasing to 13+/-1 micros at L-band. For more viscous solvent mixtures, T(2) is much shorter than T(1) and weakly frequency dependent, which indicates that incomplete motional averaging of hyperfine anisotropy makes a significant contribution to T(2). In water and 1:1 water:glycerol solutions continuous wave EPR linewidths are not relaxation determined, but become relaxation determined in the higher viscosity 1:9 water:glycerol solutions. The Lorentzian component of the 250-MHz linewidths as a function of viscosity is in good agreement with T(2)-determined contributions to the linewidths at higher frequencies.     

Measurement of proliferation activity in human melanoma xenografts by magnetic resonance imaging

Tumor proliferation may be predictive for malignant progression and response to fractionated therapy of cancer. The purpose of the present work was to investigate whether the proliferation activity of solid tumors can be assessed in vivo from the proton relaxation times, T1 and T2. Tumors of four amelanotic human melanoma xenograft lines were studied. Three parameters were used to represent tumor proliferation activity; the volume doubling time, Tvol, the potential doubling time, Tpot, and the fraction of cells in S-phase. Tvol was determined from volumetric growth data. Tpot and S-phase fraction were determined by flow cytometric analysis of tumor cells after bromodeoxyuridine (BrdU) incorporation in vivo. T1 and T2 were measured by 1H-MRI in vivo, using spin-echo pulse sequences. The proliferation parameters and relaxation times differed considerably among the tumor lines. Significant correlations were found between the proliferation parameters and the relaxation times, regardless of whether Tvol, Tpot, or S-phase fraction was considered. Tumors with short Tvol and Tpot and high S-phase fraction had long T1 and T2 compared to tumors with long Tvol and Tpot and low S-phase fraction. The elongated T1 and T2 of fast growing tumors were probably due to increased interstitial and/or intravascular water content. The present results suggest that in vivo spin-echo 1H-MRI can be used to discriminate between tumors of high and low proliferation activity.     

Quantitative dependence of MR signal intensity on tissue concentration of Gd(HP-DO3A) in the nephrectomized rat.

Cardiac-gated SE 20/224 +/- 20 MR images were obtained from nephrectomized rats before and after intravenously administering 153Gd-Gd(HP-DO3A). The concentration of Gd, [Gd], was linear in dose in myocardium, skeletal muscle, and blood. Under steady-state conditions, where d[Gd]/dt = 0, image intensities (IIN) in regions of interest were compared with the measured [Gd]. IIN was linear in myocardium at less than or equal to 0.61 mumol/g-myocardium (less than or equal to 0.5 mmol/kg dose) and in skeletal muscle at less than or equal to 0.63 mumol/g-muscle (less than or equal to 0.75 mmol/kg). Above 0.6 mumol Gd/g-tissue, IIN did not increase further. The in vivo data were consistent with measured ex vivo and in vivo relaxivities. A 29% greater slope for IIN versus [Gd] in myocardium [14,439 +/- 4350 IIN (mumol/g)] than in muscle [10,258 +/- 5,296 IIN/(mumol/g)] was attributed to a significant difference in blood content: 25% versus 2% weight blood in myocardium and skeletal muscle, respectively. Two components were apparent from plots of ex vivo 1/T1 versus [Gd] in myocardium and muscle, and only one for blood.     

Comparison of quantitative imaging of cartilage for osteoarthritis: T2, T1ρ, dGEMRIC and contrast-enhanced computed tomography

Evaluation of glycosaminoglycan (GAG) concentration in articular cartilage is of particular interest to the study of degenerative joint diseases such as osteoarthritis (OA). Noninvasive imaging techniques such as magnetic resonance imaging (MRI) and computed tomography (CT) have demonstrated the potential to assess biochemical markers of cartilage integrity such as GAG content; however, many imaging techniques are available and the optimization of particular techniques in the diagnosis of joint disease remains an active area of research. In order to highlight the differences between these various approaches, this work compares MRI (T1, T2 and T1ρ) and contrast-enhanced CT in human articular cartilage, in both the presence and absence of gadolinium-based contrast agent. Pre- and postcontrast T2 values were found to be similar on a regional level and correlated with each other. As expected, T1 values were shortened significantly on both a global and a spatial basis in the presence of gadolinium (Gd); similar results were found for T1ρ. T2 values were found to correlate mildly with postcontrast T1, T1(Gd) and with precontrast T1ρ values. In addition, contrast-enhanced CT values correlated with both precontrast T1ρ and T1(Gd) more strongly than with precontrast T2. Finally, T1(Gd) and precontrast T1ρ were found to be moderately correlated with CT data. However, T1(Gd) and precontrast T1ρ were found to be almost completely uncorrelated. Together, these results indicate that T1ρ, T2 and contrast-enhanced techniques may provide complementary information about the molecular environment in cartilage during the evolution of OA.     

Intercomparative studies of brachytherapy techniques combined with CF Boron neutron capture therapy

In this work the depth dose distribution for γ-rays, slow and fast neutrons, nuclear recoils and -particles inside a tumor phantom filled with 100 ppm ¹⁰B in distilled water was measured. The depth dose distributions were measured and represented on three-dimensional plots when a ²⁵²Cf neutron source was situated in interstitial, surface and intracavitary brachytherapy techniques. Comparison of the three brachytherapy techniques when combined with BNCT revealed that the damage induced in the tumor by the -particles as nuclear recoils in the interstitial geometry is much more than the other two techniques.     

A comparison of T2*-weighted magnitude and phase imaging for measuring the arterial input function in the rat aorta following intravenous injection of gadolinium contrast agent

The arterial input function (AIF) is important for quantitative MR imaging perfusion experiments employing Gd contrast agents. This study compared the accuracy of T(2)*-weighted magnitude and phase imaging for noninvasive measurement of the AIF in the rat aorta. Twenty-eight in vivo experiments were performed involving simultaneous arterial blood sampling and MR imaging following Gd injection. In vitro experiments were also performed to confirm the in vivo results. At 1.89 T and TE=3 ms, the relationship between changes in 1/T(2)* in blood (estimated from MR signal magnitude) and Gd concentration ([Gd]) was measured to be approximately 19 s(-1) mM(-1), while that between phase and [Gd] was approximately 0.19 rad mM(-1). Both of these values are consistent with previously published results. The in vivo phase data had approximately half as much scatter with respect to [Gd] than the in vivo magnitude data (r(2)=.34 vs. r(2)=.17, respectively). This is likely due to the fact that the estimated change in 1/T(2)* is more sensitive than the phase to a variety of factors such as partial volume effects and T(1) weighting. Therefore, this study indicates that phase imaging may be a preferred method for measuring the AIF in the rat aorta compared to T(2)*-weighted magnitude imaging.     

Lesion T(2) relaxation times and volumes predict the response of malignant breast lesions to neoadjuvant chemotherapy

The aim of this study was to investigate the utility of the water T(2) values of malignant breast lesions in predicting response after the first and second cycles of neoadjuvant chemotherapy (NAC), both alone and in combination with lesion volumes. Thirty-five patients were scanned before the commencement of chemotherapy and again after the first, second and final treatment cycles. Two methods of obtaining lesion T(2) were used: imaging, where a series of T(2)-weighted images was acquired (T(R)/T(E)=1000/30, 60, 90 and 120 ms), and spectroscopy, where the T(2) value of unsuppressed water signal was determined with a multiecho sequence (T(R)=1.5 s; initial T(E)=35 ms; 64 steps of 2.5 ms; 2 unsuppressed acquisitions per T(E)). Lesion volumes were computed from contrast-enhanced 3D fat-suppressed images. The study found that, using the imaging method of obtaining T(2), the ratio of the product of lesion T(2) and volume after the second cycle of NAC to pretreatment value is a good predictor of ultimate lesion response, defined as a > or =65% reduction in tumor volume after the final treatment cycle, with positive and negative predictive values of 95.5% and 84.6%, respectively.