MRI of tarantulas: morphological and perfusion imaging

This paper describes a study performed to evaluate the feasibility of using a 1.5-T whole-body magnetic resonance imaging (MRI) equipment, in combination with pharmacokinetic modeling, to obtain in vivo information about the morphology and perfusion of tarantulas (Eurypelma californicum). MRI was performed on three tarantulas using spin-echo sequences for morphological imaging and a rapid spoiled gradient-echo sequence for dynamic imaging during and after contrast medium (CM; Gd-DTPA) injection. Signal enhancement in dynamic measurements was evaluated with a pharmacokinetic two-compartment model. Spin-echo images showed morphological structures well. Dynamic images were of sufficient quality and allowed a model analysis of CM kinetics, which provides information about regional perfusion. In conclusion, morphological and dynamic contrast-enhanced MRI of tarantulas is feasible with a conventional clinical scanner. Studies of this kind are therefore possible without a dedicated high-field animal scanner.     

Assessment of in vitro vs. in vivo lung structure using hyperpolarized helium-3 diffusion magnetic resonance imaging

The purpose of this study was to assess the properties of a model system for hyperpolarized He-3 (HHe) diffusion MR imaging created from the lungs of New Zealand white rabbits by drying the lungs while inflated at constant pressure. The dried lungs were prepared by sacrificing the animal, harvesting the lungs en bloc and dehydrating the lungs for several days using dry compressed air. In four rabbits, the apparent diffusion coefficient (ADC) of HHe gas was measured in vivo and, within 1 week, in vitro in the dried lungs. To assess long-term repeatability, in vitro ADC values were measured again 3 months later. Dried lungs from four additional rabbits were imaged twice on the same day to assess the short-term repeatability of ADC measurements, and tissue samples from these lungs were then removed for histology. In vivo and in vitro ADC maps showed similar features and similar distributions of ADC values; mean in vivo and in vitro ADC values differed by less than 12%. The in vitro mean ADC values were highly reproducible, with no more than 5% difference between measurements for the short-term repeatability and less than 17% difference between measurements for the long-term repeatability. Histological samples from the dried lungs demonstrated that the lung structure remained intact. These results suggest that the dried lungs are a useful and inexpensive alternative to human or in vivo animal studies for HHe diffusion MR sequence development, testing and optimization.     

Assessment of extravascular extracellular space fraction in human melanoma xenografts by DCE-MRI and kinetic modeling

Tumor aggressiveness and response to therapy are influenced by the extravascular extracellular space fraction (EESF) of the malignant tissue. The EESF may, therefore, be an important prognostic parameter for cancer patients. The aim of this study was to investigate whether gadopentetate dimeglumine (Gd-DTPA)-based dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) can be used to assess the EESF of tumors. Amelanotic human melanoma xenografts (A-07, R-18) were used as preclinical models of human cancer. Images of E.F (E is the initial extraction fraction of Gd-DTPA and F is perfusion) and lambda (the partition coefficient of Gd-DTPA) were obtained by Kety analysis of DCE-MRI data. Our study was based on the hypothesis that lambda is governed by the EESF and is not influenced significantly by microvascular density (MVD) or blood perfusion. To test this hypothesis, we searched for correlations between lambda and E.F, MVD or EESF by comparing lambda images with E.F images, histological preparations from the imaged tissue and the radial heterogeneity in EESF obtained by invasive imaging. Positive correlations were found between lambda and EESF. Thus, median lambda was larger in A-07 tumors than in R-18 tumors by a factor of 4.2 (P<.00001), consistent with the histological observation that EESF is approximately fourfold larger in A-07 tumors than in R-18 tumors. The radial heterogeneity in lambda in A-07 and R-18 tumors was almost identical to the radial heterogeneity in EESF. Moreover, lambda was larger in tissue regions with high EESF than in tissue regions with low EESF in A-07 tumors (P=.048). On the other hand, significant correlations between lambda and MVD or E.F could not be detected. Consequently, Kety analysis of Gd-DTPA-based DCE-MRI series of xenografted tumors provides lambda images that primarily reflect the EESF of the tissue.     

Magnetic resonance diffusion-weighted imaging: quantitative evaluation of age-related changes in healthy liver parenchyma

The purpose of this study was to verify in healthy liver parenchyma the possible influence of age on DwI-related parameters: apparent diffusion coefficient (ADC), perfusion fraction (PF), diffusion and pseudodiffusion coefficient (D and D^?). Forty healthy adult volunteers (age range 26-86 years), divided into four age groups, were prospectively submitted to a breath-hold magnetic resonance diffusion imaging (MR-DwI) (two b values, 0-300 and 0-1000 s/mm²). A smaller cohort of 16 subjects underwent a free-breath multi-b acquisition (16 b values, 0-750 s/mm²). Quantitative analysis was performed by two observers with manually defined regions of interest, on the most homogeneous portion of the right liver lobe. Individual and group statistical analysis of data was performed: ANOVA to establish differences between groups and Pearson correlation coefficient to investigate the association between DwI parameters and age. The mean, S.D. and 95% limits of agreement of ADC values for each age-defined group are reported. ANOVA showed no significant differences between group means (P always >.05). No significant correlation between subjects' age and DwI parameters was established, both in breath-hold and free-breath acquisitions, on the whole range of adopted b values. Our study conducted on healthy liver parenchyma shows that there are no significant differences in ADC, PF, D and D^? of younger or older subjects.     

Biexponential analysis of intravoxel incoherent motion in calf muscle before and after exercise: Comparisons with arterial spin labeling perfusion and T2

PurposeThis study aimed to clarify exercise-induced changes in intravoxel incoherent motion (IVIM) parameters obtained from diffusion-weighted imaging (DWI) of the calf muscle, as well as the relationships between IVIM parameters, perfusion, and water content in muscle tissue.Materials and methodsThirteen healthy volunteers underwent IVIM-DWI, arterial spin labeling (ASL), and multi-echo spin-echo T₂ mapping of the right calf on a 3.0-T magnetic resonance imaging scanner before and after performing dorsiflexion exercise. From the data, we derived the perfusion-related diffusion coefficient (D^⁎), perfusion component fraction (F), blood flow parameter (FD^⁎), and restricted diffusion coefficient (D) in the tibialis anterior muscle. The muscle blood flow (MBF) and transverse relaxation time (T₂) were also calculated from the ASL and multi-echo spin-echo data, respectively. We compared the parameters measured before and after exercise and assessed the relationship of each IVIM-derived perfusion parameter (D^⁎, F, and FD^⁎) with MBF and each diffusion parameter (D and ADC) or F with T₂.ResultsNotably, all these parameters were significantly increased after exercise. Before exercise, the FD^⁎ exhibited a significant positive correlation with the MBF, whereas no significant correlation was observed between D^⁎ or F and MBF. After exercise, both D^⁎ and FD^⁎ exhibited significant positive correlations with MBF, whereas F was not significantly correlated with MBF. Additionally, D was significantly correlated with T₂ after exercise, but not before exercise. No significant correlations were found between ADC and T₂ either before or after exercise.ConclusionsThe IVIM analyses before and after exercise enable the simultaneous evaluation of exercise-induced changes in perfusion and water diffusion in the muscle and increases the body of information on muscle physiology.     

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.     

Associations between IVIM histogram parameters and histopathology in rectal cancer

PurposeHistogram analysis can better reflect tumor heterogeneity than conventional imaging analysis. The present study analyzed possible correlations between histogram analysis parameters derived from Intravoxel-incoherent imaging (IVIM) and histopathological features in rectal cancer (RC).MethodsSeventeen patients with histopathologically proven rectal adenocarcinomas were retrospectively acquired. In all cases, pelvic MRI was performed. Diffusion weighted imaging was obtained using a multi-slice single-shot echo-planar imaging sequence with b values of 0, 50, 200, 500 and 1000 s/mm². Simplified IVIM analysis was performed using the IntelliSpace portal, version 10 and the following images were generated: f (perfusion fraction) map, D (true diffusion coefficient) map, and ADC map utilizing all b-values. Histogram based analysis of signal intensities was performed for every IVIM map using an in-house matlab tool. Histopathology was investigated using Ki 67 specimens with calculation of Ki 67-index and cellularity. CD31 stained specimens were used for calculation of microvessel density (MVD).ResultsThere were statistically significant correlations between Ki 67 index and mode derived from ADC as well as entropy from f, r=−0.50, p=.04 and r=−0.55, p=.02, respectively. MVD correlated well with parameters derived from f.ConclusionIVIM histogram analysis parameters can reflect histopathology in RC. ADC and D values are associated with proliferation potential. Perfusion fraction f is associated with MVD.     

Effect of anesthesia on the signal intensity in tumors using BOLD-MRI: comparison with flow measurements by Laser Doppler flowmetry and oxygen measurements by luminescence-based probes

BOLD-contrast functional magnetic resonance imaging (MRI) was used to assess the evolution of tumor oxygenation and blood flow after administration of four different anesthetics: pentobarbital (60 mg/kg), ketamine/xylazine (80/8 mg/kg), fentanyl/droperidol (0.078/3.9 mg/kg), and isoflurane (1.5%). Gradient echo sequences were carried out at 4.7 Tesla in a TLT tumor model implanted in the muscle of NMRI mice. In parallel experiments, tumor blood flow and tumor pO2 were measured using the OxyLite/OxyFlo probe system. A comparison was made with the changes occurring in the skeletal muscle (host tissue). The signal intensity was dramatically decreased in tumors after administration of anesthetics, except isoflurane. These results correlated well with measurements of oxygenation and blood perfusion. Isoflurane produced constant muscle pO2 and blood perfusion although large transient fluctuations in pO2 and blood flow were reported in some tumors. Our results emphasize the need for careful monitoring of the effects of anesthesia when trying to identify new therapeutic approaches that are aimed at modulating tumor hemodynamics.     

Comparison of accuracy of intravoxel incoherent motion and apparent diffusion coefficient techniques for predicting malignancy of head and neck tumors using half-Fourier single-shot turbo spin-echo diffusion-weighted imaging

Purpose

To evaluate the use of the intravoxel incoherent motion (IVIM) technique in half-Fourier single-shot turbo spin-echo (HASTE) diffusion-weighted imaging (DWI), and to compare its accuracy to that of apparent diffusion coefficient (ADC) to predict malignancy in head and neck tumors.

Patients and methods

HASTE DW images of 33 patients with head and neck tumors (10 benign and 23 malignant) were evaluated. Using the IVIM technique, parameters (D, true diffusion coefficient; f, perfusion fraction; D*, pseudodiffusion coefficient) were calculated for each tumor. ADC values were measured over a range of b values from 0 to 1000 s/mm². IVIM parameters and ADC values in benign and malignant tumors were compared using Student's t test, receiver operating characteristics (ROC) analysis, and multivariate logistic regression modeling.

Results

Mean ADC and D values of malignant tumors were significantly lower than those of benign tumors (P < 0.05). Mean D* values of malignant tumors were significantly higher than those of benign tumors (P < 0.05). There was no significant difference in mean f values between malignant and benign tumors (P > 0.05). The technique of combining D and D* was the best for predicting malignancy; accuracy for this model was higher than that for ADC.

Conclusions

The IVIM technique may be applied in HASTE DWI as a diagnostic tool to predict malignancy in head and neck masses. The use of D and D* in combination increases the diagnostic accuracy in comparison with ADC.     

Measurement of the extracellular volume of human melanoma xenografts by contrast enhanced magnetic resonance imaging

The magnitude of the extracellular volume fraction (ECV) of tumors is of importance for the transport of macromolecular therapeutic agents from the vessel wall to the tumor cells. The aim of this study was to develop a method for measurement of tumor ECV by contrast enhanced MRI. Tumors of two human amelanotic melanoma xenograft lines (A-07 and R-18) grown intradermally in Balb/c nu/nu mice were used as model system, and muscle tissue was used as control. The renal arteries of the mice were ligated prior to i.v. administration of Gd-DTPA, and an MRI protocol for calculating Gd-DTPA concentration in tissue was followed. ECV was calculated from the Gd-DTPA concentrations in the tissue and in a plasma sample. In muscle tissue, the concentration reached a constant level after 1 min and the ECV was calculated to be 0.12 (+/- 0.01), consistent with values reported in the literature. Individual tumors showed large differences in the uptake of Gd-DTPA. The Gd-DTPA concentration in the tissue at 40 min after the Gd-DTPA administration was used to calculate tumor ECV. The ECV was found to differ significantly among regions of individual tumors and among individual tumors. The ECV ranged from 0.075 to 0.33 for A-07 tumors and from 0.016 to 0.097 for R-18 tumors. The intra- and intertumor heterogeneity in ECV was confirmed by histologic findings, showing that contrast enhanced MRI is suitable for non-invasive studies of the ECV in experimental tumors without necrosis.     

Monitoring chemotherapeutic response in RIF-1 tumors by single-quantum and triple-quantum-filtered (23)Na MRI, (1)H diffusion-weighted MRI and PET imaging

The effects of 5-fluorouracil (5FU, 150 mg/kg, ip) on subcutaneously implanted radiation-induced fibrosarcoma (RIF-1) tumors were monitored by in vivo (1)H MRI to evaluate the water apparent diffusion coefficient (ADC), by single-quantum (SQ) and triple-quantum-filtered (TQF) (23)Na MRI to evaluate compartmental Na(+) content and by positron emission tomography (PET) to evaluate 2-[(18)F]fluoro-2-deoxy-d-glucose (FDG) uptake in the tumor. The MRI experiments were performed on untreated control and treated mice once before and then daily for 3 days after treatment. The PET experiments were performed on separate groups of age- and tumor-volume-matched animals once before and then 3 days after treatment. Tumor volumes significantly decreased in treated animals 2 and 3 days posttreatment. At the same time points, in vivo MRI measurements showed an increase in both total tissue SQ (23)Na signal intensity (SI) and water ADC in treated tumors while control tumors showed no change in these parameters. TQF (23)Na SI and FDG uptake were significantly lower in treated tumors compared with control tumors 3 days after 5FU treatment. The correlated increases in total tissue (23)Na SI and water ADC following chemotherapy reflect an increase in extracellular space, while the lower TQF (23)Na SI and FDG uptake in treated tumors compared with control tumors suggest a shift in tumor metabolism from glycolysis to oxidation and/or a decrease in cell density.     

Investigating brain tumor differentiation with diffusion and perfusion metrics at 3T MRI using pattern recognition techniques

The aim of this study was to evaluate the contribution of diffusion and perfusion MR metrics in the discrimination of intracranial brain lesions at 3T MRI, and to investigate the potential diagnostic and predictive value that pattern recognition techniques may provide in tumor characterization using these metrics as classification features. Conventional MRI, diffusion weighted imaging (DWI), diffusion tensor imaging (DTI) and dynamic-susceptibility contrast imaging (DSCI) were performed on 115 patients with newly diagnosed intracranial tumors (low-and- high grade gliomas, meningiomas, solitary metastases). The Mann–Whitney U test was employed in order to identify statistical differences of the diffusion and perfusion parameters for different tumor comparisons in the intra-and peritumoral region. To assess the diagnostic contribution of these parameters, two different methods were used; the commonly used receiver operating characteristic (ROC) analysis and the more sophisticated SVM classification, and accuracy, sensitivity and specificity levels were obtained for both cases. The combination of all metrics provided the optimum diagnostic outcome. The highest predictive outcome was obtained using the SVM classification, although ROC analysis yielded high accuracies as well. It is evident that DWI/DTI and DSCI are useful techniques for tumor grading. Nevertheless, cellularity and vascularity are factors closely correlated in a non-linear way and thus difficult to evaluate and interpret through conventional methods of analysis. Hence, the combination of diffusion and perfusion metrics into a sophisticated classification scheme may provide the optimum diagnostic outcome. In conclusion, machine learning techniques may be used as an adjunctive diagnostic tool, which can be implemented into the clinical routine to optimize decision making.     

Association between visual degeneration of intervertebral discs and the apparent diffusion coefficient

The value of apparent diffusion coefficient (ADC) measurements in intervertebral disc has been studied because ADC provides an estimate of free diffusion of unbound water and could be used as a quantitative tool to estimate degenerative changes. However, the challenging nature of diffusion imaging of spine and limited numbers of subjects in earlier studies has produced contradictory findings. We aimed to determine the relation between ADC and visual degenerative changes in lumbar intervertebral discs in a sufficiently large homogeneous study group. Lumbar spines of 228 volunteer middle-aged men were MR imaged at 1.5 T including anatomic and diffusion-weighted imaging. ADC values, T2 signal intensity and height, and width of the three lowest lumbar intervertebral discs were measured and disc degeneration visually graded. The calculated average ADC of 530 measured discs was 2.01×10⁻³ mm²/s±0.29 (±S.D.). The reduction in ADC between visually normal and moderately degenerated discs was 4%. Severely degenerated discs showed 5% larger ADC values than normal discs, presumably due to free water in cracks and fissures of those discs. T2 signal intensity of the disc was significantly correlated with the ADC values, whereas other measured parameters did not show correlation. There was no evident difference in ADC between the studied anatomic lumbar levels. Because there is considerable overlap between ADC values of normal and degenerated discs, we conclude that ADC measurements of intervertebral discs, at least with current technology, have limited clinical value.     

Relationship between apparent diffusion coefficient and signal intensity in endometrial and other pelvic cysts

We evaluated whether apparent diffusion coefficient (ADC) value is more useful than signal intensity for differentiating endometrial cysts from other pelvic cysts. In an in vitro study, signal intensity and diffusion coefficients were measured in whole blood phantoms in which blood oxidation was gradually increased and concentration subsequently diluted. Although both signal intensity and diffusion value were largely affected by blood concentration, diffusion value was almost independent of blood oxidation and red blood cell lysis-related diminution of magnetic nonhomogeneity, both factors greatly affecting signal intensity on T1- and T2-weighted images. In an in vivo study, differentiation between endometrial and other pelvic cysts was attempted by means of ADC values and signal ratios of cysts to muscles on T1- and T2-weighted images (T1- and T2-ratios). Endometrial cysts tended to show lower T2-ratios, higher T1-ratios, and lower ADC values than other pelvic cysts (p < 0.001). However, ADC values were not correlated with T1- and T2-ratios (p < /0.15/). The ability of ADC value to discriminate between these two groups (discriminant rate, 91.4%) was higher than that of T2-ratio (71.4%) or T1-ratio (88.6%). If combined, ADC and T1-ratio (or T2-ratio) showed higher discriminant rate (94.3%) than the combination of T1- and T2 ratios (88.6%). ADC value might be useful for evaluating the blood concentration of a cystic lesion, because diffusion value is more closely related to blood concentration and almost independent of blood oxidation and red blood cell lysis that largely affect signal intensity.     

An evaluation of the time dependence of the anisotropy of the water diffusion tensor in acute human ischemia

We have performed MRI examinations to determine the water diffusion tensor in the brain of six patients who were admitted to the hospital within 12 h after the onset of cerebral ischemic symptoms. The examinations have been carried out immediately after admission, and thereafter at varying intervals up to 90 days post admission. Maps of the trace of the diffusion tensor, the fractional anisotropy and the lattice index, as well as maps of cerebral blood perfusion parameters, were generated to quantitatively assess the character of the water diffusion tensor in the infarcted area. In patients with significant perfusion deficits and substantial lesion volume changes, four of six cases, our measurements show a monotonic and significant decrease in the diffusion anisotropy within the ischemic lesion as a function of time. We propose that retrospective analysis of this quantity, in combination with brain tissue segmentation and cerebral perfusion maps, may be used in future studies to assess the severity of the ischemic event.     

In vivo NMR of hyperpolarized 3He in the human lung at very low magnetic fields

We present NMR measurements of the diffusion of hyperpolarized 3He in the human lung performed at fields much lower than those of conventional MRI scanners. The measurements were made on standing subjects using homebuilt apparatus operating at 3mT. O(2)-limited transverse relaxation (T(2) up to 15-35s) could be measured in vivo. Accurate global diffusion measurements have been performed in vivo and in a plastic bag; the average apparent diffusion coefficient (ADC) in vivo was 14.2+/-0.6mm(2)/s, whereas the diffusion coefficient in the bag (3He diluted in N(2)) was 79.5+/-1mm(2)/s. 1D ADC mapping with high SNR ( approximately 200-300) demonstrates the real possibility of performing quality lung imaging at extremely low fields.     

Simultaneous acquisition of perfusion and permeability from corrected relaxation rates with dynamic susceptibility contrast dual gradient echo

This study compared two methods, corrected (separation of T(1) and T(2)* effects) and uncorrected, in order to determine the suitability of the perfusion and permeability measures through Delta R(2)* and Delta R(1) analyses. A dynamic susceptibility contrast dual gradient echo (DSC-DGE) was used to image the fixed phantoms and flow phantoms (Sephadex perfusion phantoms and dialyzer phantom for the permeability measurements). The results confirmed that the corrected relaxation rate was linearly proportional to gadolinium-diethyltriamine pentaacetic acid (Gd-DTPA) concentration, whereas the uncorrected relaxation rate did not in the fixed phantom and simulation experiments. For the perfusion measurements, it was found that the correction process was necessary not only for the Delta R(1) time curve but also for the Delta R(2)* time curve analyses. Perfusion could not be measured without correcting the Delta R(2)* time curve. The water volume, which was expressed as the perfusion amount, was found to be closer to the theoretical value when using the corrected Delta R(1) curve in the calculations. However, this may occur in the low concentration of Gd-DTPA in tissue used in this study. For the permeability measurements based on the two-compartment model, the permeability factor (k(ev); e = extravascular, v = vascular) from the outside to the inside of the hollow fibers was greater in the corrected Delta R(1) method than in the uncorrected Delta R(1) method. The differences between the corrected and the uncorrected Delta R(1) values were confirmed by the simulation experiments. In conclusion, this study proposes that the correction for the relaxation rates, Delta R(2)* and Delta R(1), is indispensable in making accurate perfusion and permeability measurements, and that DSC-DGE is a useful method for obtaining information on perfusion and permeability, simultaneously.     

Quantitative assessment of Gd-DTPA contrast agent from signal enhancement: an in-vitro study

Quantitative determination of in-vivo gadolinium diethylenetriamine-pentaacid (Gd-DTPA) concentration is attractive in various studies involving perfusion, tracer kinetics and permeability constants. Using a 1.5 T clinical system and a 7 T small-bore system, we evaluated a method for absolute determination of Gd-DTPA concentrations in plasma solutions. Different solutions of Gd-DTPA and (99m)Tc-DTPA were mixed in human plasma and concentrations in the range of 0-5.0 mmol/l (1.5 T system) or 0-3.0 mmol/l (7 T system) of Gd-DTPA were divided into thirteen tubes. All MRI measurements were carried out using conventional sequences (SE, FLASH and GRASS). The MR measured intensity was converted to Gd-DTPA concentration by mathematical interpretation of the sequences. All MRI sequences showed, that the measured concentrations of Gd-DTPA revealed a slight non-linear difference compared with the calculated Gd-DTPA concentrations determined by the plasma (99m)Tc-DTPA using gamma counting. This non-linearity was most pronounced at high Gd-DTPA concentrations, suggesting that the discrepancy could be a result of an increased plasma relaxivity at higher concentrations. Adjustment of measured Gd-DTPA concentration was therefore performed using a selected power function, A[Gd-DTPA](a), which yielded the best linear relationship. Regression analysis showed that the scaling constant (A) varied from 0.11 to 97.45 and the power constant (a) varied from 0.83 to 1.6. Based on these constants, the MRI measured concentrations of Gd-DTPA did not differ from the calculated concentrations of Gd-DTPA obtained from reference measurements of (99m)Tc-DTPA. In the 1.5 T system, a linear relationship (r(2) > or = 0.95) was demonstrated in the range of 0-5.0 mmol/l Gd-DTPA, and in the 7 T system, a linear relationship (r(2) > or = 0.92) was demonstrated in the range of 0-3.0 mmol/l Gd-DTPA. Additionally, the effect of signal-to-noise on measured concentrations of Gd-DTPA was simulated using MR data of the mixed solutions of Gd-DTPA in plasma and the analytical expression of the pulse sequences. The simulations showed that the concentrations were most sensitive to noise in the GRASS sequence. In conclusion, this study demonstrates a novel approach to quantify accurately the Gd-DTPA concentration directly from MRI signal data using different routine sequences.     

Assessment of T1 time course changes and tissue-blood ratios after Gd-DTPA administration in brain tumors

Sequential T1 changes in brain tumor tissue after Gd-DTPA administration were investigated in 10 patients, including 4 meningiomas, 2 gliomas, 3 metastatic cerebral tumors and 1 brain abscess. T1 values were measured serially for 60 minutes following Gd-DTPA injection using a magnetic focusing technique. In vitro T1 of the whole blood samples was also comparatively examined. Time processes in the tissue-blood ratio (TBR) were calculated from two-point relaxation rates at 5 and 30 minutes. The obtained ratios of TBR were ranged from 1.0 to 3.0, probably depending on histological types of brain tumor (the value of 1.0 to 1.5 for meningioma and 1.5 to 3.0 for glioma and metastatic tumor). No significant changes in the T1 value were observed in the examined normal tissue and peritumoral edema. These results indicate that Gd-DTPA plays an important role not only as an image enhancer for tumor tissue but also as an indicator for estimating the blood-brain barrier function.     

Differentiation of high-grade and low-grade intra-axial brain tumors by time-dependent diffusion MRI

IntroductionOscillating gradient spin-echo (OGSE) sequences enable acquisitions with shorter diffusion times. There is growing interest in the effect of diffusion time on apparent diffusion coefficient (ADC) values in patients with cancer. However, little evidence exists regarding its usefulness for differentiating between high-grade and low-grade brain tumors. The purpose of this study is to investigate the utility of changes in the ADC value between short and long diffusion times in distinguishing low-grade and high-grade brain tumors.Material and methodsEleven patients with high-grade brain tumors and ten patients with low-grade brain tumors were scanned using a 3 T magnetic resonance imaging with diffusion-weighted imaging (DWI) using OGSE and PGSE (effective diffusion time [Δ_eff]: 6.5 ms and 35.2 ms) and b-values of 0 and 1000 s/mm². Using a region of interest (ROI) analysis of the brain tumors, we measured the ADC for two Δeff (ADC_Δeff) values and computed the subtraction ADC (ΔADC = ADC_{6.5 ms} − ADC_{35.2 ms}) and the relative ADC (ΔADC = (ADC_{6.5 ms} − ADC_{35.2 ms}) / ADC_{35.2 ms} × 100). The maximum values for the subtraction ADC (ΔADC_max) and the relative ADC (rADC_max) on the ROI were compared between low-grade and high-grade tumors using the Wilcoxon rank-sum test. A P-value <.05 was considered significant. The ROIs were also placed in the normal white matter of patients with high- and low-grade brain tumors, and ΔADC_max values were determined.ResultsHigh-grade tumors had significantly higher ΔADC_max and rADC_max than low-grade tumors. The ΔADC_max values of the normal white matter were lower than the ΔADC_max of high- and low-grade brain tumors.ConclusionThe dependence of ADC values on diffusion time between 6.5 ms and 35.2 ms was stronger in high-grade tumors than in low-grade tumors, suggesting differences in internal tissue structure. This finding highlights the importance of reporting diffusion times in ADC evaluations and might contribute to the grading of brain tumors using DWI.