Conversion of arterial input functions for dual pharmacokinetic modeling using Gd‐DTPA/MRI and 18F‐FDG/PET

Reaching the full potential of magnetic resonance imaging (MRI)‐positron emission tomography (PET) dual modality systems requires new methodologies in quantitative image analyses. In this study, methods are proposed to convert an arterial input function (AIF) derived from gadolinium‐diethylenetriaminepentaacetic acid (Gd‐DTPA) in MRI, into a ¹⁸F‐fluorodeoxyglucose (¹⁸F‐FDG) AIF in PET, and vice versa. The AIFs from both modalities were obtained from manual blood sampling in a F98‐Fisher glioblastoma rat model. They were well fitted by a convolution of a rectangular function with a biexponential clearance function. The parameters of the biexponential AIF model were found statistically different between MRI and PET. Pharmacokinetic MRI parameters such as the volume transfer constant (K^trans), the extravascular–extracellular volume fraction (ν_e), and the blood volume fraction (ν_p) calculated with the Gd‐DTPA AIF and the Gd‐DTPA AIF converted from ¹⁸F‐FDG AIF normalized with or without blood sample were not statistically different. Similarly, the tumor metabolic rates of glucose (TMRGlc) calculated with ¹⁸F‐FDG AIF and with ¹⁸F‐FDG AIF obtained from Gd‐DTPA AIF were also found not statistically different. In conclusion, only one accurate AIF would be needed for dual MRI‐PET pharmacokinetic modeling in small animal models. Magn Reson Med, 2013. © 2012 Wiley Periodicals, Inc.     

Toward local arterial input functions in dynamic contrast-enhanced MRI

Purpose

To present a method for estimating the local arterial input function (AIF) within a dynamic contrast‐enhanced MRI scan, based on the alternating minimization with model (AMM) method.

Materials and Methods

This method clusters a subset of data into representative curves, which are then input to the AMM algorithm to return a parameterized AIF and pharmacokinetic parameters. Computer simulations are used to investigate the accuracy with which the AMM is able to estimate the true AIF as a function of the input tissue curves.

Results

Simulations show that a power law relates uncertainty in kinetic parameters and SNR and heterogeneity of the input. Kinetic parameters calculated with the measured AIF are significantly different from those calculated with either a global (P < 0.005) or a local input function (P = 0.0). The use of local AIFs instead of measured AIFs yield mean lesion‐averaged parameter changes: K^trans: +24% [+15%, +70%], k_ep: +13% [?36%, +300%]. Globally estimated input functions yield mean lesion‐averaged changes: K^trans: +9% [?38%, +65%], k_ep: +13% [?100%, +400%]. The observed improvement in fit quality with local AIFs was found to be significant when additional free parameters were accounted for using the Akaike information criterion.

Conclusion

Local AIFs result in significantly different kinetic parameter values. The statistically significant improvement in fit quality suggests that changes in parameter estimates using local AIFs reflect differences in underlying tissue physiology. J. Magn. Reson. Imaging 2010;32:924–934. © 2010 Wiley‐Liss, Inc.

     

Comparison of model‐based arterial input functions for dynamic contrast‐enhanced MRI in tumor bearing rats

When using tracer kinetic modeling to analyze dynamic contrast‐enhanced MRI (DCE‐MRI) it is necessary to identify an appropriate arterial input function (AIF). The measured AIF is often poorly sampled in both clinical and preclinical MR systems due to the initial rapid increase in contrast agent concentration and the subsequent large‐scale signal change that occurs in the arteries. However, little work has been carried out to quantify the sensitivity of tracer kinetic modeling parameters to the form of AIF. Using a preclinical experimental data set, we sought to measure the effect of varying model forms of AIF on the extended Kety compartmental model parameters (K^trans, v_e, and v_p) through comparison with the results of experimentally acquired high temporal resolution AIFs. The AIF models examined have the potential to be parameterized on lower temporal resolution data to predict the form of the true, higher temporal resolution AIF. The models were also evaluated through application to the population average AIF. It was concluded that, in the instance of low temporal resolution or noisy data, it may be preferable to use a bi‐exponential model applied to the raw data AIF, or when individual measurements are not available a bi‐exponential model of the average AIF. Magn Reson Med, 2009. © 2009 Wiley‐Liss, Inc.     

Quantification of myocardial blood flow using model based analysis of first‐pass perfusion MRI: Extraction fraction of Gd‐DTPA varies with myocardial blood flow in human myocardium

For the absolute quantification of myocardial blood flow (MBF), Patlak plot‐derived K1 need to be converted to MBF by using the relation between the extraction fraction of gadolinium contrast agent and MBF. This study was conducted to determine the relation between extraction fraction of Gd‐DTPA and MBF in human heart at rest and during stress. Thirty‐four patients (19 men, mean age of 66.5 ± 11.0 years) with normal coronary arteries and no myocardial infarction were retrospectively evaluated. First‐pass myocardial perfusion MRI during adenosine triphosphate stress and at rest was performed using a dual bolus approach to correct for saturation of the blood signal. Myocardial K1 was quantified by Patlak plot method. Mean MBF was determined from coronary sinus flow measured by phase contrast cine MRI and left ventricle mass measured by cine MRI. The extraction fraction of Gd‐DTPA was calculated as the K1 divided by the mean MBF. The extraction fraction of Gd‐DTPA was 0.46 ± 0.22 at rest and 0.32 ± 0.13 during stress (P < 0.001). The relationship between extraction fraction (E) and MBF in human myocardium can be approximated as E = 1 ? exp(?(0.14 × MBF + 0.56)/MBF). The current results indicate that MBF can be accurately quantified by Patlak plot method of first‐pass myocardial perfusion MRI by performing a correction of extraction fraction. Magn Reson Med, 2011. © 2011 Wiley Periodicals, Inc.     

Assessment of fast dynamic imaging and the use of Gd‐EOB‐DTPA for MR‐guided liver interventions

Purpose:

1) To analyze and compare fast dynamic imaging sequences to biopsy suspect liver lesions. 2) To evaluate the additional use of hepatocyte‐specific contrast agent compared to the nonenhanced fast dynamic scans and diagnostic liver imaging.

Materials and Methods:

Image acquisition was performed using a 1T open‐configured scanner suitable for interventional purposes. Transversal postcontrast T1‐weighted (T1w) fat‐saturated 3D high‐resolution examination (THRIVE) images were acquired >20 minutes postintravenous application of gadolinium ethoxybenzyl diethylenetriaminepentaacetic acid (Gd‐EOB‐DTPA). A single slice, crossing the level of the lesion, was acquired using intermediate‐weighted steady‐state free‐precession (bTFE), T1w‐gradient echo and spin echo (T1FFE/TSE), T2w‐spin echo (sshTSE) sequences. T1w imaging was acquired prior and after contrast media application. Diagnostic and fast dynamic images were compared based on a 10‐point rating scale. In addition, the liver‐to‐lesion‐contrast ratio was measured.

Results:

A total of 39 malignant lesions with a mean diameter of 13 mm (5–30 mm) in 39 patients were included. Concerning a test of noninferiority, there was no significant difference between rating score values of fast dynamic imaging employing contrast‐enhanced T1FFE‐sequences compared to diagnostic THRIVE (P = 0.001). Calculated liver‐to‐lesion contrast also showed no difference for either imaging sequence (P = 1.0). All other sequences tested showed significant inferiority (P ≤ 0.001).

Conclusion:

T1w Gd‐EOB‐DTPA contrast‐enhanced fast dynamic GRE imaging significantly improves the contrast behavior of malignant liver lesions comparable to diagnostic imaging and is best suited for liver intervention, especially at 1T open magnetic resonance imaging. J. Magn. Reson. Imaging 2011;. © 2011 Wiley‐Liss, Inc.     

Variation of the relaxographic “shutter‐speed” for transcytolemmal water exchange affects the CR bolus‐tracking curve shape

Contrast reagents (CRs) may enter the tissue interstitium for a period after a vascular bolus injection. As the amount of interstitial CR increases, the longitudinal relaxographic NMR “shutter‐speed” (T ^–1) for the equilibrium transcytolemmal water exchange process increases. The quantity T ^–1 is given by |r_1o[CR_o] + R_1o0 – R_1i| (where r_1o and [CR_o] represent the interstitial (extracellular) CR relaxivity and concentration, respectively, and R_1o0 and R_1i are the extra‐ and intracellular ¹H₂O relaxation rate constants, respectively, in the absence of exchange). The increase of T ^–1 with [CR_o] causes the kinetics of the water exchange equilibrium to appear to decrease. Here, analytical theory for two‐site‐exchange processes is combined with that for pharmacokinetic CR delivery, extraction, and distribution in a method termed BOLus Enhanced Relaxation Overview (BOLERO^©). The shutter‐speed effect alters the shape of the bolus‐tracking (B‐T) time‐course. It is shown that this is mostly accounted for by the inclusion of only one additional parameter, which measures the mean intracellular lifetime of a water molecule. Simulated and real data demonstrate that the effect of shutter‐speed variation on pharmacokinetic parameters can be very significant: neglecting this effect can lead to an underestimation of the parameter values by 50%. This phenomenon can be heterogeneous. Within a tiny gliosarcoma implanted in the rat brain, the interstitial CR in the tumor core never rises to a level sufficient to cause apparent slowing of the exchange process. However, within the few microns needed to reach the proliferating rim, this occurs to a significant degree. Thus, even relative pharmacokinetic quantities can be incorrectly represented in a parametric map that neglects this effect. The BOLERO analysis shows promise for in vivo vascular phenotyping in pathophysiology. It also includes a provision for approximating the separation of the perfusion and permeability contributions to CR extravasation. Magn Reson Med 50:1151–1169, 2003. © 2003 Wiley‐Liss, Inc.     

Effects of artery input function on dynamic contrast-enhanced MRI for determining grades of gliomas

Objective:To evaluate the effect of artery input function (AIF) derived from different arteries for pharmacokinetic modeling on dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) parameters in the grading of gliomas.Methods:49 patients with pathologically confirmed gliomas were recruited and underwent DCE-MRI. A modified Tofts model with different AIFs derived from anterior cerebral artery (ACA), ipsilateral and contralateral middle cerebral artery (MCA) and posterior cerebral artery (PCA) was used to estimate quantitative parameters such as K^trans (volume transfer constant) and V_e (fractional extracellular-extravascular space volume) for distinguishing the low grade glioma from high grade glioma. The K^trans and V_e were compared between different arteries using Two Related Samples Tests (TRST) (i.e. Wilcoxon Signed Ranks Test). In addition, these parameters were compared between the low and high grades as well as between the grade II and III using the Mann-Whitney U-test. A p-value of less than 0.05 was regarded as statistically significant.Results:All the patients completed the DCE-MRI successfully. Sharp wash-in and wash-out phases were observed in all AIFs derived from the different arteries. The quantitative parameters (K^trans and V_e) calculated from PCA were significant higher than those from ACA and MCA for low and high grades, respectively (p < 0.05). Despite the differences of quantitative parameters derived from ACA, MCA and PCA, the K^trans and V_e from any AIFs could distinguish between low and high grade, however, only K^trans from any AIFs could distinguish grades II and III. There was no significant correlation between parameters and the distance from the artery, which the AIF was extracted, to the tumor.Conclusion:Both quantitative parameters K^trans and V_e calculated using any AIF of ACA, MCA, and PCA can be used for distinguishing the low- from high-grade gliomas, however, only K^trans can distinguish grades II and III.Advances in knowledge:We sought to assess the effect of AIF on DCE-MRI for determining grades of gliomas. Both quantitative parameters K^trans and V_e calculated using any AIF of ACA, MCA, and PCA can be used for distinguishing the low- from high-grade gliomas.     

Blind estimation of the arterial input function in dynamic contrast‐enhanced MRI using purity maximization

Uncertainty in arterial input function (AIF) estimation is one of the major errors in the quantification of dynamic contrast‐enhanced MRI. A blind source separation algorithm was proposed to determine the AIF by selecting the voxel time course with maximum purity, which represents a minimal contamination from partial volume effects. Simulations were performed to assess the partial volume effect on the purity of AIF, the estimation accuracy of the AIF, and the influence of purity on the derived kinetic parameters. In vivo data were acquired from six patients with hypopharyngeal cancer and eight rats with brain tumor. Results showed that in simulation the AIF with the highest purity is closest to the true AIF. In patients, the manually selection had reduced purity, which could lead to underestimations of K^trans and V_e and an overestimation of V_p when compared with those obtained by the proposed blind source separation algorithm. The derived kinetic parameters in the tumor were more susceptible to the changes in purity when compared with those in the muscle. The animal experiment demonstrated good reproducibility in blind source separation‐AIF derived parameters. In conclusion, the blind source separation method is feasible and reproducible to identify the voxel with the tracer concentration time course closest to the true AIF. Magn Reson Med, 2012. © 2012 Wiley Periodicals, Inc.     

Extended graphical model for analysis of dynamic contrast‐enhanced MRI

Kinetic analysis with mathematical models has become increasingly important to quantify physiological parameters in computed tomography (CT), positron emission tomography (PET), and dynamic contrast‐enhanced MRI (DCE‐MRI). The modified Kety/Tofts model and the graphical (Patlak) model have been widely applied to DCE‐MRI results in disease processes such as cancer, inflammation, and ischemia. In this article, an intermediate model between the modified Kety/Tofts and Patlak models is derived from a mathematical expansion of the modified Kety/Tofts model. Simulations and an in vivo experiment involving DCE‐MRI of carotid atherosclerosis were used to compare the new extended graphical model with the modified Kety/Tofts model and the Patlak model. In our simulated circumstances and the carotid artery application, we found that the extended graphical model exhibited lower noise sensitivity and provided more accurate estimates of the volume transfer constant (K^trans) and fractional plasma volume (v_p) than the modified Kety/Tofts model for DCE‐MRI acquisitions of total duration less than 100–300 s, depending on kinetic parameters. In comparison with the Patlak model, we found that the extended graphical model exhibited 74.4–99.8% less bias in estimates of K^trans. Thus, the extended graphical model may allow kinetic modeling of DCE‐MRI results with shortened data acquisition periods, without sacrificing accuracy in estimates of K^trans and v_p. Magn Reson Med, 2011. © 2011 Wiley‐Liss, Inc.     

Phase‐based arterial input function measurements in the femoral arteries for quantification of dynamic contrast‐enhanced (DCE) MRI and comparison with DCE‐CT

Dynamic contrast‐enhanced (DCE) MRI is useful for diagnosis, treatment monitoring and follow‐up of prostate cancer. However, large differences have been reported in the parameter range of the transfer constant K^trans, making longitudinal studies and comparison of DCE‐MRI findings between studies difficult. Large part of this inconsistency in K^trans values can be attributed to problems with the accurate measurement of the arterial input function (AIF) from the magnitude signal (AIF_MAGN). Phase‐based AIF measurements (AIF_PHASE) have been proposed as a more robust alternative to AIF_MAGN measurements. This study compares AIF_PHASE with AIFs measured with DCE‐CT (AIF_CT), and the corresponding K^trans maps in 12 prostate cancer patients. The shape of AIF_PHASE and AIF_CT are similar, although differences in the peak height and peak width exist as a result of differences in injection protocol. No significant differences in K^trans values were found between the DCE‐MRI and DCE‐CT exams, with median K^trans values of 0.10 and 0.08 min^?1 for healthy peripheral zone tissue and 0.44 and 0.36 min^?1 for regions suspected of tumor respectively. Therefore, robust quantification of K^trans values from DCE‐MRI exams in the cancerous prostate is feasible with the use of AIF_PHASE. Magn Reson Med, 2011. © 2011 Wiley Periodicals, Inc.     

Model‐based blind estimation of kinetic parameters in dynamic contrast enhanced (DCE)‐MRI

A method to simultaneously estimate the arterial input function (AIF) and pharmacokinetic model parameters from dynamic contrast‐enhanced (DCE)‐MRI data was developed. This algorithm uses a parameterized functional form to model the AIF and k‐means clustering to classify tissue time‐concentration measurements into a set of characteristic curves. An iterative blind estimation algorithm alternately estimated parameters for the input function and the pharmacokinetic model. Computer simulations were used to investigate the algorithm's sensitivity to noise and initial estimates. In 12 patients with sarcomas, pharmacokinetic parameter estimates were compared with “truth” obtained from model regression using a measured AIF. When arterial voxels were included in the blind estimation algorithm, the resulting AIF was similar to the measured input function. The “true” K^trans values in tumor regions were not significantly different than the estimated values, 0.99 ± 0.41 and 0.86 ± 0.40 min^?1, respectively, P = 0.27. “True” k_ep values also matched closely, 0.70 ± 0.24 and 0.65 ± 0.25 min^?1, P = 0.08. When only tissue curves free of significant vascular contribution are used (v_p < 0.05), the resulting AIF showed substantial delay and dispersion consistent with a more local AIF such as has been observed in dynamic susceptibility contrast imaging in the brain. Magn Reson Med, 2009. © 2009 Wiley‐Liss, Inc.     

Arterial input functions determined from MR signal magnitude and phase for quantitative dynamic contrast‐enhanced MRI in the human pelvis

Dynamic contrast‐enhanced (DCE) MRI is often used to measure the transfer constant (K^trans) and distribution volume (v_e) in pelvic tumors. For optimal accuracy and reproducibility, one must quantify the arterial input function (AIF). Unfortunately, this is challenging due to inflow and signal saturation. A potential solution is to use MR signal phase (?), which is relatively unaffected by these factors. We hypothesized that phase‐derived AIFs (AIF_?) would provide more reproducible K^trans and v_e values than magnitude‐derived AIFs (AIF_|S|). We tested this in 27 prostate dynamic contrast‐enhanced MRI studies (echo time = 2.56 ms, temporal resolution = 13.5 s), using muscle as a standard. AIF_? peak amplitude varied much less as a function of measurement location (inferior–superior) than AIF_|S| (5.6 ± 0.6 mM vs. 2.6 ± 1.5 mM), likely as a result of ? inflow insensitivity. However, our main hypothesis was not confirmed. The best AIF_|S| provided similar reproducibility versus AIF_? (interpatient muscle K^trans = 0.039 ± 0.021 min^?1 vs. 0.037 ± 0.025 min^?1, v_e = 0.090 ± 0.041 vs. 0.062 ± 0.022, respectively). Magn Reson Med, 2011. © 2011 Wiley‐Liss, Inc.     

Dynamic contrast‐enhanced magnetic resonance imaging of abdominal solid organ and major vessel: Comparison of enhancement effect between Gd‐EOB‐DTPA and Gd‐DTPA

Purpose

To evaluate the differences in enhancement of the abdominal solid organ and the major vessel on dynamic contrast‐enhanced magnetic resonance imaging (DCE‐MRI) obtained with gadolinium ethoxybenzyldiethylenetriamine pentaacetic acid (Gd‐EOB‐DTPA: EOB) and gadolinium diethylenetriamine pentaacetic acid (Gd‐DTPA) in the same patients.

Materials and Methods

A total of 13 healthy volunteers underwent repeat assessments of abdominal MR examinations with DCE‐MRI using either Gd‐DTPA at a dose of 0.1 mmol/kg body weight or EOB at a dose of 0.025 mmol/kg body weight. DCE images were obtained at precontrast injection and in the arterial phase (AP: 25 seconds), portal phase (PP: 70 seconds), and equilibrium phase (EP: 3 minutes). The signal intensities (SIs) of liver at AP, PP, and EP; the SIs of spleen, renal cortex, renal medulla, pancreas, adrenal gland, aorta at AP; and the SIs of portal vein and inferior vena cava (IVC) at PP were defined using region‐of‐interest measurements, and were used for calculation of signal intensity ratio (SIR).

Results

The mean SIRs of liver (0.195 ± 0.140), spleen (1.35 ± 0.353), renal cortex (1.58 ± 0.517), renal medulla (0.548 ± 0.259), pancreas (0.540 ± 0.183), adrenal gland (1.04 ± 0.405), and aorta (2.44 ± 0.648) at AP as well as the mean SIRs of portal vein (1.85 ± 0.477) and IVC (1.16 ± 0.187) at PP in the EOB images were significantly lower than those (0.337 ± 0.200, 1.99 ± 0.443, 2.01 ± 0.474, 0.742 ± 0.336, 0.771 ± 0.227, 1.26 ± 0.442, 3.22 ± 1.20, 2.73 ± 0.429, and 1.68 ± 0.366, respectively) in the Gd‐DTPA images (P < 0.05 each). There was no significant difference in mean SIR of liver at PP between EOB (0.529 ± 0.124) and Gd‐DTPA (0.564 ± 0.139). Conversely, the mean SIR of liver at EP was significantly higher with EOB (0.576 ± 0.167) than with Gd‐DTPA (0.396 ± 0.093) (P < 0.001).

Conclusion

Lower arterial vascular and parenchymal enhancement with Gd‐EOB, as compared with Gd‐DTPA, may require reassessment of its dose, despite the higher late venous phase liver parenchymal enhancement. J. Magn. Reson. Imaging 2009;29:636–640. © 2009 Wiley‐Liss, Inc.     

Assessment of liver function in thioacetamide‐induced rat acute liver injury using an empirical mathematical model and dynamic contrast‐enhanced MRI with Gd‐EOB‐DTPA

Purpose:

To evaluate thioacetamide (TAA)‐induced acute liver injury in rats using an empirical mathematical model (EMM) and dynamic contrast‐enhanced magnetic resonance imaging (DCE‐MRI) with gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd‐EOB‐DTPA).

Materials and Methods:

Eighteen rats were divided into three groups (normal control [n = 6], TAA [140] [n = 6], and TAA [280] groups [n = 6]). The rats of the TAA (140) and TAA (280) groups were intravenously injected with 140 and 280 mg/kg body weight (BW) of TAA, respectively, while those of the normal control group were intravenously injected with the same volume of saline. DCE‐MRI studies were performed using Gd‐EOB‐DTPA (0.025 mmol Gd/kg; 0.1 mL/kg BW) as the contrast agent 48 hours after TAA or saline injection. After the DCE‐MRI study, blood was sampled and serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were measured. We calculated the rate of contrast uptake (α), the rate of contrast washout (β), the elimination half‐life of relative enhancement (RE) (T_1/2), the maximum RE (RE_max), and the time to (RE_max) (T_max) from time‐signal intensity curves using EMM.

Results:

The RE_max values in the TAA (140) groups and TAA (280) groups were significantly smaller than that in the normal control group. The T_max value in the TAA (280) group was significantly greater than that in the normal control group. The β value in the TAA (280) group was significantly smaller than those in the normal control and TAA (140) groups, whereas there were no significant differences in β among groups. The T_1/2 value in the TAA (280) group was significantly greater than those in the normal control and TAA (140) groups. The RE_max, T_max, β, and T_1/2 values significantly correlated with AST and ALT.

Conclusion:

The EMM is useful for evaluating TAA‐induced acute liver injury using DCE‐MRI with Gd‐EOB‐DTPA. J. Magn. Reson. Imaging 2012; 36:1483–1489. © 2012 Wiley Periodicals, Inc.     

Photoreceptor degeneration changes magnetic resonance imaging features in a mouse model of retinitis pigmentosa

Retinal degeneration‐1 (rd1) mice are animal models of retinitis pigmentosa, a blinding disease caused by photoreceptor cell degeneration. This study aims to determine magnetic resonance imaging (MRI) changes in retinas of 1‐ and 3‐month‐old rd1 mice. Apparent diffusion coefficient in retina was measured using diffusion MRI. The blood‐retinal barrier leakage was evaluated using gadolinium‐diethylenetriaminepentaacetic acid‐enhanced T₁‐weighted MRI before and after systemic gadolinium‐diethylenetriaminepentaacetic acid injection. Photoreceptor degeneration in rd1 retina was apparent by decreased retinal thickness and loss of water diffusion anisotropy in both 1‐ and 3‐month‐old rd1 mice. Furthermore, statistically significant increase of mean retinal apparent diffusion coefficient and gadolinium‐diethylenetriaminepentaacetic acid‐enhanced T₁‐weighted MRI signals were observed in 3‐month‐old rd1 mice comparing with age‐matched wild‐type mice. Together, these data suggest that MRI parameter changes can signature common pathological changes in photoreceptor‐degenerated eyes, particularly blood‐retinal barrier leakage‐induced retinal edema. Magn Reson Med, 2011. © 2011 Wiley‐Liss, Inc.     

Dynamic contrast‐enhanced‐MRI of tumor hypoxia

Patients with highly hypoxic primary tumors show increased frequency of locoregional treatment failure and poor survival rates and may benefit from particularly aggressive treatment. The potential of gadolinium diethylene‐triamine penta‐acetic acid‐based dynamic contrast‐enhanced‐MRI in assessing tumor hypoxia was investigated in this preclinical study. Xenografted tumors of eight human melanoma lines were subjected to dynamic contrast‐enhanced‐MRI and measurement of the fraction of radiobiologically hypoxic cells and the fraction of pimonidazole‐positive hypoxic cells. Tumor images of K^trans (the volume transfer constant of gadolinium diethylene‐triamine penta‐acetic acid) and v_e (the fractional distribution volume of gadolinium diethylene‐triamine penta‐acetic acid) were produced by pharmacokinetic analysis of the dynamic contrast‐enhanced‐MRI data, and K^trans and v_e frequency distributions of the non‐necrotic tumor tissue were established and related to the extent of hypoxia. Tumors showing high K^trans values and high v_e values had low fractions of hypoxic cells, whereas tumors showing both low K^trans values and low v_e values had high hypoxic fractions. K^trans differentiated better between tumors with low and high hypoxic fractions than did v_e. This study supports the current attempts to establish dynamic contrast‐enhanced‐MRI as a method for assessing the extent of hypoxia in human tumors, and it provides guidelines for the clinical development of valid assays. Magn Reson Med, 2012. © 2011 Wiley Periodicals, Inc.     

Correction of arterial input function in dynamic contrast-enhanced MRI of the liver

Purpose:

To develop a postprocessing method to correct saturation of arterial input function (AIF) in T1‐weighted dynamic contrast‐enhanced magnetic resonance imaging (DCE‐MRI) for quantification of hepatic perfusion.

Materials and Methods:

The saturated AIF is corrected by parameterizing the first pass of the AIF as a smooth function with a single peak and minimizing a least‐squares error in fitting the liver DCE‐MRI data to a dual‐input single‐compartment model. Sensitivities of the method to the degree of saturation in the AIF first‐pass peak and the image contrast‐to‐noise ratio were assessed. The method was also evaluated by correlating portal venous perfusion with an independent overall liver function measurement.

Results:

The proposed method corrects the distorted AIF with a saturation ratio up to 0.45. The corrected AIF improved hepatic arterial perfusion by ?23.4% and portal venous perfusion by 26.9% in a study of 12 patients with liver cancers. The correlation between the mean voxelwise portal venous perfusion and overall liver function measurement was improved by using the corrected AIFs (R² = 0.67) compared with the saturated AIFs (R² = 0.39).

Conclusion:

The method is robust for correcting AIF distortion and has the potential to improve quantification of hepatic perfusion for assessment of liver tissue response to treatment in patients with hepatic cancers. J. Magn. Reson. Imaging 2012;36:411–421. © 2012 Wiley Periodicals, Inc.

     

Feasibility of shutter‐speed DCE‐MRI for improved prostate cancer detection

The feasibility of shutter‐speed model dynamic‐contrast‐enhanced MRI pharmacokinetic analyses for prostate cancer detection was investigated in a prebiopsy patient cohort. Differences of results from the fast‐exchange‐regime‐allowed (FXR‐a) shutter‐speed model version and the fast‐exchange‐limit‐constrained (FXL‐c) standard model are demonstrated. Although the spatial information is more limited, postdynamic‐contrast‐enhanced MRI biopsy specimens were also examined. The MRI results were correlated with the biopsy pathology findings. Of all the model parameters, region‐of‐interest‐averaged K^trans difference [ΔK^trans ≡ K^trans(FXR‐a) ? K^trans(FXL‐c)] or two‐dimensional K^trans(FXR‐a) vs. k_ep(FXR‐a) values were found to provide the most useful biomarkers for malignant/benign prostate tissue discrimination (at 100% sensitivity for a population of 13, the specificity is 88%) and disease burden determination. (The best specificity for the fast‐exchange‐limit‐constrained analysis is 63%, with the two‐dimensional plot.) K^trans and k_ep are each measures of passive transcapillary contrast reagent transfer rate constants. Parameter value increases with shutter‐speed model (relative to standard model) analysis are larger in malignant foci than in normal‐appearing glandular tissue. Pathology analyses verify the shutter‐speed model (FXR‐a) promise for prostate cancer detection. Parametric mapping may further improve pharmacokinetic biomarker performance. Magn Reson Med, 2013. © 2012 Wiley Periodicals, Inc.     

Progression of experimental lesions of atherosclerosis: Assessment by kinetic modeling of black‐blood dynamic contrast‐enhanced MRI

Pharmacokinetic modeling of dynamic contrast‐enhanced (DCE) magnetic resonance imaging (MRI) is used to noninvasively characterize neovasculature and inflammation in atherosclerotic vessels by estimating perfusion characteristics, such as fractional plasma volume v_p and transfer constant K^trans. DCE‐MRI has potential to study the evolution of nascent lesions involving early pathological changes. However, currently used bright‐blood DCE‐MRI approaches are difficult to apply to small lesions because of the difficulty in separating the signal in the thin vessel wall from the adjacent lumen. By suppressing the lumen signal, black‐blood DCE‐MRI techniques potentially provide a better tool for early atherosclerotic lesion assessment. However, whether black‐blood DCE‐MRI can detect temporal changes in physiological kinetic parameters has not been investigated for atherosclerosis. This study of balloon‐injured New Zealand White rabbits used a reference‐region‐based pharmacokinetic model of black‐blood DCE‐MRI to evaluate temporal changes in early experimental atherosclerotic lesions of the abdominal aorta. Six rabbits were imaged at 3 and 6 months after injury. K^trans was found to increase from 0.10 ± 0.03 min^?1 to 0.14 ± 0.05 min^?1 (P = 0.01). In histological analysis of all twelve rabbits, K^trans showed a significant correlation with macrophage content (R = 0.70, P =0.01). These results suggest black‐blood DCE‐MRI and a reference‐region kinetic model could be used to study plaque development and therapeutic response in vivo. Magn Reson Med, 2013. © 2012 Wiley Periodicals, Inc.     

Sampling requirements in DCE‐MRI based analysis of high grade gliomas: Simulations and clinical results

Purpose:

To investigate the effect of variations in temporal resolution and total measurement times on the estimations of kinetic parameters derived from dynamic contrast‐enhanced (DCE) MRI in patients with high‐grade gliomas (HGGs).

Materials and Methods:

DCE‐MRI with high temporal resolution (dynamic sampling time (T_s) = 2.1 s and 3.4 s) and total sampling time (T_acq) of 5.2 min was acquired in 101 examinations from 15 patients. Using the modified Tofts model K^trans, k_ep v_e and v_p were estimated. The effects of increasing T_s and reducing T_acq on the estimated kinetic parameters were estimated through down‐sampling and data truncation, and the results were compared with numerical simulations.

Results:

There was an overall dependence of all four kinetic parameters on T_s and T_acq. Increasing T_s resulted in under‐estimation of K^trans and over‐estimation of V_p, whereas k_ep and V_e varied in a less predictable manner. Reducing T_acq resulted in over‐estimation of K^trans and k_ep and under‐estimation of v_p and v_e. Increasing T_s and reducing T_acq resulted in increased relative error for all four parameters.

Conclusion:

Estimated K^trans, K_ep, and V_e in HGGs were within 15% of the high sampling rate reference values for T_s<20 s. Increasing T_s and reducing T_acq leads to reduced precision of the estimated values. J. Magn. Reson. Imaging 2013;37:818–829. © 2012 Wiley Periodicals, Inc.