Dynamic Contrast-enhanced Magnetic Resonance Imaging Protocol Research Articles

Systematic evaluation of MRI-based characterization of tumor-associated vascular morphology and hemodynamics via a dynamic digital phantom.

Validation of quantitative imaging biomarkers is a challenging task, due to the difficulty in measuring the ground truth of the target biological process. A digital phantom-based framework is established to systematically validate the quantitative characterization of tumor-associated vascular morphology and hemodynamics based on dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). A digital phantom is employed to provide a ground-truth vascular system within which 45 synthetic tumors are simulated. Morphological analysis is performed on high-spatial resolution DCE-MRI data (spatial/temporal resolution = 30 to ) to determine the accuracy of locating the arterial inputs of tumor-associated vessels (TAVs). Hemodynamic analysis is then performed on the combination of high-spatial resolution and high-temporal resolution (spatial/temporal resolution = 60 to to 10s) DCE-MRI data, determining the accuracy of estimating tumor-associated blood pressure, vascular extraction rate, interstitial pressure, and interstitial flow velocity. The observed effects of acquisition settings demonstrate that, when optimizing the DCE-MRI protocol for the morphological analysis, increasing the spatial resolution is helpful but not necessary, as the location and arterial input of TAVs can be recovered with high accuracy even with the lowest investigated spatial resolution. When optimizing the DCE-MRI protocol for hemodynamic analysis, increasing the spatial resolution of the images used for vessel segmentation is essential, and the spatial and temporal resolutions of the images used for the kinetic parameter fitting require simultaneous optimization. An in silico validation framework was generated to systematically quantify the effects of image acquisition settings on the ability to accurately estimate tumor-associated characteristics.

7T dynamic contrast-enhanced MRI for the detection of subtle blood-brain barrier leakage.

Background and PurposeDynamic contrast‐enhanced MRI (DCE‐MRI) can be employed to assess the blood–brain barrier (BBB) integrity. Detection of BBB leakage at lower field strengths (≤3T) is cumbersome as the signal is noisy, while leakage can be subtle. Utilizing the increased signal‐to‐noise ratio at higher field strengths, we explored the application of 7T DCE‐MRI for assessing BBB leakage.MethodsA dual‐time resolution DCE‐MRI method was implemented at 7T and a slow injection rate (0.3 ml/s) and low dose (3 mmol) served to obtain signal changes linearly related to the gadolinium concentration, that is, minimized for T2 * degradation effects. With the Patlak graphical approach, the leakage rate (Ki ) and blood plasma volume fraction (vp ) were calculated. The method was evaluated in 10 controls, an ischemic stroke patient, and a patient with a transient ischemic attack.Results Ki and vp were significantly higher in gray matter compared to white matter of all participants. These Ki values were higher in both patients compared to the control subjects. Finally, for the lesion identified in the ischemic stroke patient, higher leakage values were observed compared to normal‐appearing tissue.ConclusionWe demonstrate how a dual‐time resolution DCE‐MRI protocol at 7T, with administration of half the clinically used contrast agent dose, can be used for assessing subtle BBB leakage. Although the feasibility of DCE‐MRI for assessing the BBB integrity at 3T is well known, we showed that a continuous sampling DCE‐MRI method tailored for 7T is also capable of assessing leakage with a high sensitivity over a range of Ki values.

Mapping of CSF transport using high spatiotemporal resolution dynamic contrast-enhanced MRI in mice: Effect of anesthesia.

Dynamic contrast-enhanced MRI (DCE-MRI) represents the only available approach for glymphatic cerebrospinal fluid (CSF) flow 3D mapping in the brain of living animals and humans. The purpose of this study was to develop a novel DCE-MRI protocol for mapping of the glymphatic system transport with improved spatiotemporal resolution, and to validate the new protocol by comparing the transport in mice anesthetized with either isoflurane or ketamine/xylazine. The contrast agent, gadobutrol, was administered into the CSF of the cisterna magna and its transport visualized continuously on a 9.4T preclinical scanner using 3D fast-imaging with a steady-state free-precession sequence (3D-FISP), which has a spatial resolution of 0.001 mm3 and a temporal resolution of 30 s. The MR signals were measured dynamically for 60 min in multiple volumes of interest covering the entire CSF space and brain parenchyma. The results confirm earlier findings that glymphatic CSF influx is higher under ketamine/xylazine than with isoflurane anesthesia. This was extended to account for new details about the distinct CSF efflux pathways under the two anesthetic regimens. Dynamic contrast MR shows that CSF clearance occurs mainly along the vagus nerve near the jugular vein under isoflurane and via the olfactory bulb under ketamine/xylazine. The improved spatial and temporal sampling rates afforded by 3D-FISP shed new light on the pharmacological modulation of CSF efflux paths. The present observations may have the potential to set a new standard for future experimental DCE-MRI studies of the glymphatic system.

Extended perfusion protocol for MS lesion quantification.

This study aims to examine a time-extended dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) protocol and report a comparative study with three different pharmacokinetic (PK) models, for accurate determination of subtle blood–brain barrier (BBB) disruption in patients with multiple sclerosis (MS). This time-extended DCE-MRI perfusion protocol, called Snaps, was applied on 24 active demyelinating lesions of 12 MS patients. Statistical analysis was performed for both protocols through three different PK models. The Snaps protocol achieved triple the window time of perfusion observation by extending the magnetic resonance acquisition time by less than 2 min on average for all patients. In addition, the statistical analysis in terms of adj-R 2 goodness of fit demonstrated that the Snaps protocol outperformed the conventional DCE-MRI protocol by detecting 49% more pixels on average. The exclusive pixels identified from the Snaps protocol lie in the low k trans range, potentially reflecting areas with subtle BBB disruption. Finally, the extended Tofts model was found to have the highest fitting accuracy for both analyzed protocols. The previously proposed time-extended DCE protocol, called Snaps, provides additional temporal perfusion information at the expense of a minimal extension of the conventional DCE acquisition time.

Clinical Implementation of a Free-Breathing, Motion-Robust Dynamic Contrast-Enhanced MRI Protocol to Evaluate Pleural Tumors.

OBJECTIVE. The purpose of this study was to develop a motion insensitive clinical dynamic contrast-enhanced MRI (DCE-MRI) protocol to assess the response of pleural tumors in clinical trials. MATERIALS AND METHODS. Thirty-two patients with pleura-based lesions were administered contrast material and imaged with gradient-recalled echo DCE-MRI sequence variants: either a traditional cartesian k-space acquisition (FLASH), a time-resolved imaging with stochastic trajectories acquisition (TWIST), or a radial stack-of-stars acquisition (radial) sequence in addition to other standard-of-care imaging sequences. Each image acquisition's sensitivity to motion was evaluated by comparing the motion of the thoracic border in 3D throughout the acquisition. One-way ANOVA was used to compare the image quality between different acquisitions. The 95% CIs were calculated for mean thoracic border displacement. The effects of motion on kinetic parameter estimation were explored with simulations according to clinically acquired data. RESULTS. Radial was the most motion-robust sequence with subvoxel mean displacement in the superior-inferior direction (0.4 ± 1.2 [SD] mm). FLASH showed intermediate displacement (4.6 ± 2.0 mm), whereas TWIST was most sensitive to motion (6.4 ± 3.4 mm). Signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) of the images acquired with the radial sequence were on par or better than the FLASH and TWIST sequences when reconstructed with an improved density compensation algorithm. Simulations showed that motion on scans showing pleural-based lesions can lead to markedly inaccurate kinetic parameter estimation and inappropriate kinetic model convergence within a nested model analysis. CONCLUSION. A practical radial k-space trajectory sequence that provides motion-insensitive pharmacokinetic parameters was incorporated as part of the DCE-MRI protocol of pleural tumors. Validation and usefulness in clinical trials assessing response to therapy is needed.

Using Dynamic Contrast-enhanced MRI as an Imaging Biomarker for Migraine: Proceed with Caution

Using Dynamic Contrast-enhanced MRI as an Imaging Biomarker for Migraine: Proceed with Caution

Hepatic function imaging using dynamic Gd-EOB-DTPA enhanced MRI and pharmacokinetic modeling.

To determine whether pharmacokinetic modeling parameters with different output assumptions of dynamic contrast-enhanced MRI (DCE-MRI) using Gd-EOB-DTPA correlate with serum-based liver function tests, and compare the goodness of fit of the different output assumptions. A 6-min DCE-MRI protocol was performed in 38 patients. Four dual-input two-compartment models with different output assumptions and a published one-compartment model were used to calculate hepatic function parameters. The Akaike information criterion fitting error was used to evaluate the goodness of fit. Imaging-based hepatic function parameters were compared with blood chemistry using correlation with multiple comparison correction. The dual-input two-compartment model assuming venous flow equals arterial flow plus portal venous flow and no bile duct output better described the liver tissue enhancement with low fitting error and high correlation with blood chemistry. The relative uptake rate Kir derived from this model was found to be significantly correlated with direct bilirubin (r = -0.52, P = 0.015), prealbumin concentration (r = 0.58, P = 0.015), and prothrombin time (r = -0.51, P = 0.026). It is feasible to evaluate hepatic function by proper output assumptions. The relative uptake rate has the potential to serve as a biomarker of function. Magn Reson Med 78:1488-1495, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

DCE-MRI-Derived Parameters in Evaluating Abraxane-Induced Early Vascular Response and the Effectiveness of Its Synergistic Interaction with Cisplatin.

Our previous studies revealed molecular alterations of tumor vessels, varying from immature to mature alterations, resulting from Abraxane, and demonstrated that the integrin-specific PET tracer 18F-FPPRGD2 can be used to noninvasively monitor such changes. However, changes in the tumor vasculature at functional levels such as perfusion and permeability are also important for monitoring Abraxane treatment outcomes in patients with cancer. The purpose of this study is to further investigate the vascular response during Abraxane therapy and the effectiveness of its synergistic interaction with cisplatin using Dynamic contrast enhanced-magnetic resonance imaging (DCE-MRI). Thirty MDA-MB-435 tumor mice were randomized into three groups: PBS control (C group), Abraxane only (A group), and sequential treatment with Abraxane followed by cisplatin (A-P group). Tumor volume was monitored based on caliper measurements. A DCE-MRI protocol was performed at baseline and day 3. The Ktrans, Kep and Ve were calculated and compared with CD31, α-SMA, and Ki67 histology data. Sequential treatment with Abraxane followed by cisplatin produced a significantly greater inhibition of tumor growth during the three weeks of the observation period. Decreases in Ktrans and Kep for the A and A-P groups were observed on day 3. Immunohistological staining suggested vascular remodeling during the Abraxane therapy. The changes in Ktrans and Kep values were correlated with alterations in the permeability of the tumor vasculature induced by the Abraxane treatment. In conclusion, Abraxane-mediated permeability variations in tumor vasculature can be quantitatively visualized by DCE-MRI, making this a useful method for studying the effects of early cancer treatment, especially the early vascular response. Vascular remodeling by Abraxane improves the efficiency of cisplatin delivery and thus results in a favorable treatment outcome.

Abstract P1-01-07: Quantitative assessment of early- and delayed DCE-MRI background parenchymal enhancement in breast cancer risk prediction

Abstract Purpose Background parenchymal enhancement (BPE) estimated from breast dynamic contrast enhanced MRI (DCE-MRI) has been correlated with breast cancer risk. Multiple time-point post-contrast-subtracted sequences are acquired in typical clinical breast DCE-MRI protocols. We quantitatively assessed BPE using fully automated computer algorithms and investigated the relationship between BPE quantified from three time-point post-contrast sequences and breast cancer risk prediction. Materials and Methods A retrospective case-control study was performed using breast DCE-MRI scans from 102 patients (mean 47.2±7.3 YO) who underwent either open surgical biopsy or core biopsy from 2009-2011: 51 women had unilateral breast cancer and 51 were age- and date-of-MRI matched controls with a unilateral biopsy-proven benign. For each MRI scan, three post-contrast-subtracted sequences (i.e., SUB 1, SUB 2 and SUB 3) acquired over a total of 7 minutes were analyzed. BPE was quantified from each of the sequences using fully automated computer algorithms on the breasts contralateral to the cancers and the contralateral (negative) breasts of the controls. For each sequence, two quantitative BPE measures were generated: the absolute BPE volume (|BPE|) and its relative amount over the whole breast volume (BPE%). Volumetric absolute and relative amounts of fibroglandular tissue (|FGT| and FGT%) were also automatically quantified, from the pre-contrast sequence. BI-RADS breast density assessment was retrieved from the mammography report (< 6 months) prior to cancer diagnosis (for cases) or MRI (for controls). Multivariable conditional logistic regression was performed to assess BPE measures, quantified respectively from SUB 1, SUB 2, and SUB 3, as predictors of breast cancer risk. Results Breast cancer risk odds ratios (ORs) were reported by |BPE| and BPE% (Table 1), after adjustment for breast density, |FGT|, and FGT%. Breast density did not correlate with risk for breast cancer in this study cohort: OR for BI-RADS density alone was 0.75 (95% CI: 0.35, 1.59; p=0.5). OR was 1.14 (95% CI: 0. 72, 1.81; p=0.6) for |FGT| alone and 0.70 (95% CI: 0.19, 2.52; p=0.6) for FGT% alone. Table 1: Breast cancer risk odds ratios (ORs) with 95% confidence intervals [CIs] for BPE quantified from SUB 1, SUB 2, and SUB 3, respectively. BPE from SUB1BPE from SUB2BPE from SUB3|BPE|2.0 (95% CI: 1.1-3.7; p=0.02)2.0 (95% CI: 1.2-3.3; p=0.01)1.7 (95% CI: 1.1-2.7; p=0.02)BPE%3.6 (95% CI: 1.3-10.1; p=0.01)2.8 (95% CI: 1.3-6.2; p=0.01)2.4 (95% CI: 1.2-5.0; p=0.02) Conclusions Increased BPE quantified from DCE-MRI are predictive of breast cancer risk, independent of measures of breast density and FGT. BPE estimated from three time-point SUB sequences has a similar predictive effect of breast cancer risk, while an early sequence (e.g., SUB 1) appears to have a larger magnitude of effect than that of a delayed sequence (e.g., SUB 3). Clinical Relevance Quantified BPE in breast DCE-MRI has potential for use as a biomarker of breast cancer risk and may be included to improve breast cancer risk prediction. A single post-contrast sequence (i.e., SUB 1) may be adequate for use to estimate breast cancer risk using breast MRI in the context of breast cancer screening for high-risk women. Citation Format: Shandong Wu, Wendie A Berg, Margarita L Zuley, Brenda F Kurland, Rachel C Jankowitz, Jules Sumkin, Robert M Nishikawa, David Gur. Quantitative assessment of early- and delayed DCE-MRI background parenchymal enhancement in breast cancer risk prediction [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P1-01-07.

Vitamin C supplementation ameliorates the adverse effects of nicotine on placental hemodynamics and histology in nonhuman primates

We previously demonstrated that prenatal nicotine exposure decreases neonatal pulmonary function in nonhuman primates, and maternal vitamin C supplementation attenuates these deleterious effects. However, the effect of nicotine on placental perfusion and development is not fully understood. This study utilizes noninvasive imaging techniques and histological analysis in a nonhuman primate model to test the hypothesis that prenatal nicotine exposure adversely effects placental hemodynamics and development but is ameliorated by vitamin C. Time-mated macaques (n = 27) were divided into 4 treatment groups: control (n = 5), nicotine only (n = 4), vitamin C only (n = 9), and nicotine plus vitamin C (n = 9). Nicotine animals received 2 mg/kg per day of nicotine bitartrate (approximately 0.7 mg/kg per day free nicotine levels in pregnant human smokers) from days 26 to 160 (term, 168 days). Vitamin C groups received ascorbic acid at 50, 100, or 250 mg/kg per day with or without nicotine. All underwent placental dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) at 135-140 days and Doppler ultrasound at 155 days to measure uterine artery and umbilical vein velocimetry and diameter to calculate uterine artery volume blood flow and placental volume blood flow. Animals were delivered by cesarean delivery at 160 days. A novel DCE-MRI protocol was utilized to calculate placental perfusion from maternal spiral arteries. Placental tissue was processed for histopathology. Placental volume blood flow was significantly reduced in nicotine-only animals compared with controls and nicotine plus vitamin C groups (P = .03). Maternal placental blood flow was not different between experimental groups by DCE-MRI, ranging from 0.75 to 1.94 mL/mL per minute (P = .93). Placental histology showed increased numbers of villous cytotrophoblast cell islands (P < .05) and increased syncytiotrophoblast sprouting (P < .001) in nicotine-only animals, which was mitigated by vitamin C. Prenatal nicotine exposure significantly decreased fetal blood supply via reduced placental volume blood flow, which corresponded with placental histological findings previously associated with cigarette smoking. Vitamin C supplementation mitigated the harmful effects of prenatal nicotine exposure on placental hemodynamics and development, suggesting that its use may limit some of the adverse effects associated with smoking during pregnancy.

Breast DCE-MRI: Influence of Postcontrast Timing on Automated Lesion Kinetics Assessments and Discrimination of Benign and Malignant Lesions

Breast dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) scanning protocols vary widely. The purpose of this study was to determine the effects of postcontrast timing on delayed-phase lesion kinetics assessment and ability to discriminate malignant from benign lesions. Following institutional review board approval, we retrospectively reviewed all lesions assessed on magnetic resonance examinations from April 2005 to June 2006. DCE-MRI was performed with 90-second temporal resolution. Delayed-phase kinetic parameters including percentages of persistent, plateau, and washout, and categorizations of predominant and worst curve type were compared between 4.5 and 7.5 minutes postcontrast. Ability to discriminate benign and malignant lesions based on delayed-phase kinetic parameters was compared between postcontrast timings by receiver operating characteristic (ROC) analysis. Two hundred eighty consecutive breast lesions (206 malignant and 74 benign) were evaluated in 228 women. Comparing kinetics assessments at 7.5 versus 4.5 minutes: volume percentage of washout increased in malignancies by a mean of 9.4% (P<.0001) and increased slightly in benign lesions (mean 3.2%, P=.007); predominant curve type categorizations changed significantly only for malignancies (P<.0001); and worst curve categorizations did not change significantly for either benign or malignant lesions (P>.05). There were no significant differences between timings in area under ROC curves for delayed-phase kinetic parameters. The choice of delayed postcontrast timing more strongly affects the kinetics assessments for malignancies than benign breast lesions, but our results suggest that a shortened breast DCE-MRI protocol may not significantly impact diagnostic accuracy. Furthermore, worst curve type classifications are least affected by postcontrast timing and may provide reliable assessment of delayed-phase kinetics across protocols.

Potential of computer‐aided diagnosis of high spectral and spatial resolution (HiSS) MRI in the classification of breast lesions

To compare the performance of computer-aided diagnosis (CADx) analysis of precontrast high spectral and spatial resolution (HiSS) MRI to that of clinical dynamic contrast-enhanced MRI (DCE-MRI) in the diagnostic classification of breast lesions. Thirty-four malignant and seven benign lesions were scanned using two-dimensional (2D) HiSS and clinical 4D DCE-MRI protocols. Lesions were automatically segmented. Morphological features were calculated for HiSS, whereas both morphological and kinetic features were calculated for DCE-MRI. After stepwise feature selection, Bayesian artificial neural networks merged selected features, and receiver operating characteristic (ROC) analysis evaluated the performance with leave-one-lesion-out validation. AUC (area under the ROC curve) values of 0.92 ± 0.06 and 0.90 ± 0.05 were obtained using CADx on HiSS and DCE-MRI, respectively, in the task of classifying benign and malignant lesions. While we failed to show that the higher HiSS performance was significantly better than DCE-MRI, noninferiority testing confirmed that HiSS was not worse than DCE-MRI. CADx of HiSS (without contrast) performed similarly to CADx on clinical DCE-MRI; thus, computerized analysis of HiSS may provide sufficient information for diagnostic classification. The results are clinically important for patients in whom contrast agent is contra-indicated. Even in the limited acquisition mode of 2D single slice HiSS, by using quantitative image analysis to extract characteristics from the HiSS images, similar performance levels were obtained as compared with those from current clinical 4D DCE-MRI. As HiSS acquisitions become possible in 3D, CADx methods can also be applied. Because HiSS and DCE-MRI are based on different contrast mechanisms, the use of the two protocols in combination may increase diagnostic accuracy.

Optimizing MRI scan time in the computation of pharmacokinetic parameters (Ktrans) in breast cancer diagnosis

To assess the effects of reduced scan time in dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) of breast for the evaluation of pharmacokinetic parameters (K(trans) , ve , and kep ). High temporal resolution DCE-MRI was performed for calculation of pharmacokinetic parameters (K(trans) , ve , and kep ) at different timepoints using an in-house developed computation scheme adopting the standard model (SM). The receiver operating characteristic (ROC) curve analysis revealed an area under the ROC curve (AUC) of 0.994 for K(trans) at 90 seconds and 0.987 for K(trans) at 60 seconds with a significant decrease in the AUC for K(trans) at 30 seconds (0.669). While ve showed a consistently higher AUC (>0.9) at timepoints ≥40 seconds, the AUC for kep showed a consistent decline with reduced acquisition times. Reducing the acquisition time for the K(trans) and ve measurement up to 60 seconds yields reasonable accuracy for both and can be incorporated in the routine DCE-MRI protocol for evaluation of enhancing breast lesions.

Preliminary Experience Using Dynamic MRI at 3.0 Tesla for Evaluation of Soft Tissue Tumors

ObjectiveWe aimed to evaluate the use of dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) at 3.0 T for differentiating the benign from malignant soft tissue tumors. Also we aimed to assess whether the shorter length of DCE-MRI protocols are adequate, and to evaluate the effect of temporal resolution.Materials and MethodsDynamic contrast-enhanced magnetic resonance imaging, at 3.0 T with a 1 second temporal resolution in 13 patients with pathologically confirmed soft tissue tumors, was analyzed. Visual assessment of time-signal curves, subtraction images, maximal relative enhancement at the first (maximal peak enhancement [Emax]/1) and second (Emax/2) minutes, Emax, steepest slope calculated by using various time intervals (5, 30, 60 seconds), and the start of dynamic enhancement were analyzed.ResultsThe 13 tumors were comprised of seven benign and six malignant soft tissue neoplasms. Washout on time-signal curves was seen on three (50%) malignant tumors and one (14%) benign one. The most discriminating DCE-MRI parameter was the steepest slope calculated, by using at 5-second intervals, followed by Emax/1 and Emax/2. All of the steepest slope values occurred within 2 minutes of the dynamic study. Start of dynamic enhancement did not show a significant difference, but no malignant tumor rendered a value greater than 14 seconds.ConclusionThe steepest slope and early relative enhancement have the potential for differentiating benign from malignant soft tissue tumors. Short-length rather than long-length DCE-MRI protocol may be adequate for our purpose. The steepest slope parameters require a short temporal resolution, while maximal peak enhancement parameter may be more optimal for a longer temporal resolution.

Abstract 274: In Vivo Assessment of Adventitial Vasa Vasorum in Patients with Symptomatic Carotid Plaques: A Dynamic Contrast-Enhanced MR Imaging Study

Objectives: To characterize adventitial vasa vasorum (VV) in unilaterally symptomatic patients and evaluate its association with intraplaque hemorrhage (IPH) and symptom status. Background: Adventitial VV is thought to be a primary source of IPH and a potential marker for plaque instability. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) has been shown capable of quantifying adventitial VV in the carotid artery. Methods: Patients with ischemic cerebrovascular symptoms within the past 6 months and ipsilateral carotid plaques underwent MR imaging examination, which included a multi-contrast protocol for detecting IPH and a DCE-MRI protocol for measuring adventitial VV. Both the symptomatic and contralateral asymptomatic arteries were studied. Adventitial VV was measured at consecutive slices as adventitial Ktrans from kinetic modeling. Maximum adventitial Ktrans across all slices were calculated for each artery. Results: From the 27 patients (22 men; 69±10 years) recruited, 50 arteries had adventitial Ktrans measurements. IPH arteries (0.142±0.042 vs. 0.112±0.029 min-1, p&lt;0.001) and symptomatic arteries (0.134±0.038 vs. 0.107±0.027 min-1, p=0.001) were shown to have higher adventitial Ktrans compared to their counterparts. In multivariate analysis, IPH, symptom status and male sex were independently associated with adventitial Ktrans. Conclusions: Adventitial VV demonstrated significant associations with IPH and symptom status. In vivo assessment of adventitial VV by DCE-MRI may be useful in studying plaque pathogenesis or risk stratification, but further examination through prospective studies is needed.

Development and characterization of a dynamic lesion phantom for the quantitative evaluation of dynamic contrast-enhanced MRI.

To develop a dynamic lesion phantom that is capable of producing physiological kinetic curves representative of those seen in human dynamic contrast-enhanced MRI (DCE-MRI) data. The objective of this phantom is to provide a platform for the quantitative comparison of DCE-MRI protocols to aid in the standardization and optimization of breast DCE-MRI. The dynamic lesion consists of a hollow, plastic mold with inlet and outlet tubes to allow flow of a contrast agent solution through the lesion over time. Border shape of the lesion can be controlled using the lesion mold production method. The configuration of the inlet and outlet tubes was determined using fluid transfer simulations. The total fluid flow rate was determined using x-ray images of the lesion for four different flow rates (0.25, 0.5, 1.0, and 1.5 ml/s) to evaluate the resultant kinetic curve shape and homogeneity of the contrast agent distribution in the dynamic lesion. High spatial and temporal resolution x-ray measurements were used to estimate the true kinetic curve behavior in the dynamic lesion for benign and malignant example curves. DCE-MRI example data were acquired of the dynamic phantom using a clinical protocol. The optimal inlet and outlet tube configuration for the lesion molds was two inlet molds separated by 30° and a single outlet tube directly between the two inlet tubes. X-ray measurements indicated that 1.0 ml/s was an appropriate total fluid flow rate and provided truth for comparison with MRI data of kinetic curves representative of benign and malignant lesions. DCE-MRI data demonstrated the ability of the phantom to produce realistic kinetic curves. The authors have constructed a dynamic lesion phantom, demonstrated its ability to produce physiological kinetic curves, and provided estimations of its true kinetic curve behavior. This lesion phantom provides a tool for the quantitative evaluation of DCE-MRI protocols, which may lead to improved discrimination of breast cancer lesions.

A comparison of tracer kinetic models for T 1 -weighted dynamic contrast-enhanced MRI: Application in carcinoma of the cervix

The Tofts tracer kinetic models are often used to analyze dynamic contrast-enhanced MRI data. They are derived from a general two-compartment exchange model (2CXM) but assume negligible plasma mean transit time. The 2CXM estimates tissue plasma perfusion and capillary permeability-surface area; the Tofts models estimate the transfer constant K(trans), which reflects a combination of these two parameters. The aims of this study were to compare the 2CXM and Tofts models and report microvascular parameters in patients with cervical cancer. Thirty patients were scanned pretreatment using a dynamic contrast-enhanced MRI protocol with a 3 sec temporal resolution and a total scan duration of 4 min. Whole-tumor parameters were estimated with both models. The 2CXM provided superior fits to the data for all patients (all 30 P values < 0.005), and significantly different parameter estimates were obtained (P < 0.01). K(trans) (mean = 0.35 +/- 0.26 min(-1)) did not equal absolute values of tissue plasma perfusion (mean = 0.65 +/- 0.56 mL/mL/min) or permeability-surface area (mean = 0.14 +/- 0.09 mL/mL/min) but correlated strongly with tissue plasma perfusion (r = 0.944; P = 0.01). Average plasma mean transit time, calculated with the 2CXM, was 22 +/- 16 sec, suggesting the assumption of negligible plasma mean transit time is not appropriate in this dataset and the 2CXM is better suited for its analysis than the Tofts models. The results demonstrate the importance of selecting an appropriate tracer kinetic model in dynamic contrast-enhanced MRI.

Abstract C128: Protocol optimization for dynamic contrast enhanced-MRI in combination with kinetic modeling

Abstract Introduction: Dynamic contrast enhanced-MRI (DCE-MRI) is increasingly used in combination with pharmacokinetic modelling (PKM) for tumor diagnosis, treatment planning and for the evaluation of novel antiangiogenic therapies. In vivo monitoring of drug response requires high reproducibility of the PKM-technique, especially for the Tofts-model prior parameter Ktrans, a measure for tumor vessel wall permeability. However, several clinical studies show high in-patient-variability and poor reproducibility of Ktrans in paired examinations, partially caused by improper experiment design. The aim of this study is to develop and to test a theoretical framework in which the uncertainty on Ktrans for a given DCE-MRI-protocol can be evaluated a priori, and the optimal values of imaging parameters, to achieve maximal reproducibility, can be determined. Methods: The DCE-MRI protocol under investigation consists of a series Turbo-Flash-images (Ti = 560 ms, flip angle = 12°, Te = 4.12 ms) with variable temporal resolution (Tr = Δt = 1–10 s) and total scan time (Tscan = 250 – 2000 s) after injection of Gd-DTPA (Dose = 0.1 mM kg−1). The a priori uncertainty on Ktrans is tested by means of the Cramer-Rao lower bounds (CRLB), a concept from system theory that predicts the minimal standard deviation σK of the fitted parameters for a given protocol design. In the first part of this study, these CRLB are used for testing the reproducibility of the protocol theoretically and selecting the optimal values for Δt and Tscan. In these simulations SNR of the MR-measurements varies as ∼√Δt. In the second part the protocols are compared experimentally. Two groups of two test animals (mice with induced ht29 - tumors) were imaged in paired examinations (36 hours in between) for 2000 s with Δt =1.1 s (group 1) and Δt = 3.3 s (group 2) respectively. For each animal and both examinations, 4 values of Ktrans are calculated (after 250 s , 500 s, 1000 s and 2000 s). The coefficient of within patient variation (CWV) is used as reproducibility measure. Results: Simulations show that for Gd-DTPA Ktrans-values between 0.02 and 0.5 min−1 can be measured with acceptable errors (K ∼ 10%, SNR =10 at t = 5 s). In this range, temporal resolution should be as high as possible (1–3 s), even if this implies reduced SNR. A minimal scan time of 1000 s is required. Low Ktrans (∼0.005 min−1) cannot be determined in a reproducible manner for Tscan &amp;lt; 5000 s, while high Ktrans (&amp;gt; 1 min−1) are inaccurate due to nyquist considerations (K &amp;gt; 50%). The in vivo experiments show similar trends: with all mean Ktrans in the range of 0.015 to 0.37 min−1, the CWV decreases with increasing scantime (group 1: 26% - 24% - 18% - 14%, group 2: 30% - 28 % - 20% -15% , Tscan = 250s - 500s -1000s -2500s). The reproducibility in group 1 is higher than in group 2 for all values of Tscan , as predicted by the Cramer-Rao theory. Conclusion: The CRLB offer an excellent framework for testing protocol design with respect to reproducibility demands. For Gd-DTPA, Ktrans-values in the range of 0.02 and 0.5 min−1 can be determined in a reproducible manner for protocols with high temporal resolution and prolonged scan time. In vivo experiments confirm the theoretical findings, showing that the CRLB can be applied for further optimization of the DCE-MRI protocol. A potential application is the assessment of optimal values of the inversion time Ti and the Gd-DTPA- dose, each within their respective bounds. Citation Information: Mol Cancer Ther 2009;8(12 Suppl):C128.

Usefulness of diffusion-weighted imaging and dynamic contrast-enhanced magnetic resonance imaging in the diagnosis of prostate transition-zone cancer

Conventional T2-weighted (T2-WI) magnetic resonance imaging (MRI) has poor sensitivity for prostate transition-zone (TZ) cancer detection. To retrospectively evaluate the clinical value of diffusion-weighted MRI (DW-MRI) and dynamic contrast-enhanced MRI (DCE-MRI) in combination with T2-WI for the diagnosis of TZ cancer. Twenty-six TZ cancers in 23 patients with at least one tumor (tumor size >10 mm) located predominantly in the TZ were included in the study. Sixteen peripheral-zone (PZ) cancers in 12 patients with PZ cancer but without TZ cancer (control group) were selected by step-section pathologic maps. All patients underwent MRI and radical prostatectomy. MRI was obtained by a 1.5T superconducting system with a phased-array coil. Imaging sequences were T2-WI with fat saturation (FST2-WI), DW-MRI (single-shot echoplanar image, b=0 and 1000 s/mm(2), apparent diffusion coefficient [ADC] map findings), and DCE-MRI (3D fast spoiled gradient recalled [SPGR], contrast medium [0.2 mmol/kg], total injection time 5 s, image acquisition 30, 60, and 90 s). Sensitivity, specificity, accuracy, and positive predictive value (PPV) for the diagnosis of TZ cancer were evaluated in four protocols: A) FST2-WI alone, B) FST2-WI plus DW-MRI, C) FST2-WI plus DCE-MRI, D) FST2-WI plus DW-MRI plus DCE-MRI. Sensitivity, specificity, accuracy, and PPV in protocol A (FST2-WI alone) were 61.5%, 68.8%, 64.3%, and 76.2%, respectively. FST2-WI plus DW-MRI (protocol B) improved the sensitivity, specificity, accuracy, and PPV. In FST2-WI plus DW-MRI plus DCE-MRI (protocol D), the number of true-negative lesions increased and false-positive lesions decreased, and the sensitivity, specificity, accuracy, and PPV were 69.2%, 93.8%, 78.6%, and 94.7%, respectively. There was a significant difference between protocols A and D (P<0.05). Adding DW-MRI to FST2-WI in the diagnosis of prostate TZ cancer increased the diagnostic accuracy. The addition of DCE-MRI may be an option to improve the specificity and PPV of diagnosing TZ cancer with FST2-WI and DW-MRI.

Diffusion-weighted and dynamic contrast-enhanced imaging as markers of clinical behavior in children with optic pathway glioma

Optic pathway gliomas (OPGs) are common pediatric brain tumors that pose significant clinical challenges with regard to predicting which tumors are likely to become symptomatic and require treatment. These tumors can arise sporadically or in the context of the inherited cancer predisposition syndrome neurofibromatosis type 1 (NF1). Few studies have suggested biological or imaging markers that predict the clinical course of this disease. In this cross-sectional study, we hypothesized that the clinical behavior of OPGs in children can be differentiated by diffusion-weighted (DW) and dynamic contrast-enhanced (DCE) MRI. A total of 27 children with OPG were studied using DW and DCE MRI protocols. Diffusivity and permeability were calculated and correlated with the clinical behavior the OPG. Mean diffusivity values of 1.39 microm2/ms and mean permeability values of 2.10 ml/min per 100 cm3 of tissue were measured. Clinically aggressive OPGs had significantly higher mean permeability values (P = 0.05) than clinically stable tumors. In addition, there was a strong correlation between clinical aggressiveness and the absence of NF1 (P < 0.01). These results suggest that DCE MRI might be a useful biomarker for clinically aggressive OPG, which should be confirmed in larger prospective longitudinal studies.