Dynamic Contrast-enhanced Measurements Research Articles

Dynamic Contrast-Enhanced MRI in Abdominal Aortic Aneurysms as a Potential Marker for Disease Progression.

Abdominal aortic aneurysms (AAAs) may rupture before reaching maximum diameter (Dmax ) thresholds for repair. Aortic wall microvasculature has been associated with elastin content and rupture sites in specimens, but its relation to progression is unknown. To investigate whether dynamic contrast-enhanced (DCE) MRI of AAA is associated with Dmax or growth. Prospective. A total of 27 male patients with infrarenal AAA (mean age ± standard deviation=75 ± 5 years) under surveillance with DCE MRI and 2 years of prior follow-up intervals with computed tomography (CT) or MRI. A 3-T, dynamic three-dimensional (3D) fast gradient-echo stack-of-stars volumetric interpolated breath-hold examination (Star-VIBE). Wall voxels were manually segmented in two consecutive slices at the level of Dmax . We measured slope to 1-minute and area under the curve (AUC) to 1 minute and 4 minutes of the signal intensity change postcontrast relative to that precontrast arrival, and, Ktrans , a measure of microvascular permeability, using the Patlak model. These were averaged over all wall voxels for association to Dmax and growth rate, and, over left/right and anterior/posterior quadrants for testing circumferential homogeneity. Dmax was measured orthogonal to the aortic centerline and growth rate was calculated by linear fit of Dmax measurements. Pearson correlation and linear mixed effects models. A P value <0.05 was considered statistically significant. In 44 DCE MRIs, mean Dmax was 45 ± 7 mm and growth rate in 1.5 ± 0.4 years of prior follow-up was 1.7 ± 1.2 mm per year. DCE measurements correlated with each other (Pearson r=0.39-0.99) and significantly differed between anterior/posterior versus left/right quadrants. DCE measurements were not significantly associated with Dmax (P=0.084, 0.289, 0.054 and 0.255 for slope, AUC at 1minute and 4 minutes, and Ktrans , respectively). Slope and 4 minutes AUC significantly associated with growth rate after controlling for Dmax . Contrast uptake may be increased in lateral aspects of the AAA. Contrast enhancement 1-minute slope and 4-minutes AUC may be associated with a period of recent AAA growth that is independent of Dmax . 3. Stage 2.

106: Novel MRI detection of impaired placental blood flow and fetal oxygen reserve in a non-human primate model of gestational protein restriction

We have recently developed novel placenta-specific MRI protocols to estimate placental oxygen reserve using blood oxygenation levels (T2* imaging). High oxyhemoglobin concentration has long T2* and correlates with areas of high perfusion as validated by dynamic contrast enhanced (DCE) MRI. Short T2* relates to areas of high deoxyhemoglobin concentration. Here our objective was to evaluate the adverse effects of maternal malnutrition on placental oxygen reserve and placental perfusion in vivo in a non-human primate model of gestational protein restriction (PR). Rhesus macaques were fed a control diet (CON, 26% protein, n=8) or switched to either a 33% PR (17% protein, n=8) or 50% PR (13% protein, n=8) diet before and during pregnancy. All underwent Doppler ultrasound (D-US) and fetal biometry measurements followed by MRI consisting of T2* and DCE measurements at gestational day 85 (G85) and G135 (term is G168). D-US was used to measure uterine artery (Uta) and umbilical vein velocimetry and diameter to calculate Uta volume blood flow (cQuta) and placental volume blood flow (cQuv). Pregnancy loss rates were 0/8 in controls, 1/8 in 33% PR, and 3/8 in 50% PR (1 prior to G135). Animals fed a 50%PR diet had significantly smaller fetal abdominal circumference (G135) and lower cQuta (G135) and cQuv (G85 and G135) versus CON (Fig 1). Additionally, by DCE-MRI, placental blood flow was significantly lower at G135 in animals fed a 50% PR diet (Fig 1). Distributions of T2* throughout the placenta (Fig 2) show significant global reductions in T2* (blood oxyhemoglobin) in animals fed a 50% PR diet vs. CON (G85 and G135). These data from a relevant translational model demonstrate that a 50% gestational PR diet reduces maternal placental perfusion, decreases fetal oxygen availability and increases fetal mortality. However, animals fed a 33% PR diet were similar to CON suggesting that placental reserve capacity is able to compensate for some PR, but not a 50% reduction. The perturbations observed with placental blood flow and fetal oxygen availability may explain the noted increased risk of human growth restriction and stillbirth with severe PR diets in the developing world. Our imaging abilities have allowed early identification of pregnancies affected by placental dysfunction and is a first step in improving outcomes.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

First trimester alcohol exposure alters placental perfusion and fetal oxygen availability affecting fetal growth and development in a non-human primate model

Prenatal alcohol exposure leads to impaired fetal growth, brain development, and stillbirth. Placental impairment likely contributes to these adverse outcomes, but the mechanisms and specific vasoactive effects of alcohol that links altered placental function to impaired fetal development remain areas of active research. Recently, we developed magnetic resonance imaging techniques in nonhuman primates to characterize placental blood oxygenation through measurements of T2* and perfusion using dynamic contrast-enhanced magnetic resonance imaging. The objective of this study was to evaluate the effects of first-trimester alcohol exposure on macaque placental function and to characterize fetal brain development invivo. Timed-pregnant Rhesus macaques (n=12) were divided into 2 groups: control (n=6) and ethanol exposed (n=6). Animals were trained to self-administer orally either 1.5 g/kg/d of a 4% ethanol solution (equivalent to 6 drinks/d) or an isocaloric control fluid from preconception until gestational day 60 (term is G168). All animals underwent Doppler ultrasound scanning followed by magnetic resonance imaging that consisted of T2* and dynamic contrast-enhanced measurements. Doppler ultrasound scanning was used to measure uterine artery and umbilical vein velocimetry and diameter to calculate uterine artery volume blood flow and placental volume blood flow. After noninvasive imaging, animals underwent cesarean delivery for placenta collection and fetal necropsy at gestational day 110 (n=6) or 135 (n=6). Fetal weight and biparietal diameter were significantly smaller in ethanol-exposed animals compared with control animals at gestational day 110. By Doppler ultrasound scanning, placental volume blood flow was significantly lower (P=.04) at gestational day 110 in ethanol-exposed vs control animals. A significant reduction in placental blood flow was evident by dynamic contrast-enhanced magnetic resonance imaging. As we demonstrated recently, T2* values vary throughout the placenta and reveal gradients in blood deoxyhemoglobin concentration that range from highly oxygenated blood (long T2*) proximal to spiral arteries to highly deoxygenated blood (short T2*). Distributions ofT2*throughout the placenta show significant global reduction in T2* (andhence high blood deoxyhemoglobin concentration) in ethanol-exposed vs control animals at gestational day 110 (P=.02). Fetal brain measurements indicated impaired growth and development at gestational day 110, but less so at gestational day 135 in ethanol-exposed vs control animals. Chronic first-trimester ethanol exposure significantly reduces placental perfusion and oxygen supply to the fetal vasculature later in pregnancy. These perturbations of placental function are associated with fetal growth impairments. However, differences between ethanol-exposed and control animals in placental function and fetal developmental outcomes were smaller at gestational day 135 than at gestational day 110. These findings are consistent with placental adaptation to early perturbations that allow for compensated placental function and maintenance of fetal growth.

Quantitative diffusion-weighted imaging and dynamic contrast-enhanced characterization of the index lesion with multiparametric MRI in prostate cancer patients.

To compare a simplified intravoxel incoherent motion (sIVIM) model to commonly used monoexponential and biexponential models in the characterization of prostate cancer (PCa) and noncancerous prostate tissues, and to investigate combinations of diffusion-weighted imaging (DWI) measures with dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI)-derived parameters in MRI-visible index lesions, to facilitate PCa risk stratification. In this retrospective, Institutional Review Board (IRB)-approved study, 43 consecutive patients with PCa who had 3T MRI exams followed by radical prostatectomy were included. DWI and DCE parameters were measured from one index lesion per patient, and noncancerous central gland and peripheral zone. Logistic regression modeling was performed to select the optimal combination of DWI and DCE measurements for tumor risk assessment. All diffusion models showed the lowest diffusion coefficients in tumors, intermediate values in noncancerous central gland, and highest values in noncancerous peripheral zone (all P < 0.001). Ktrans and kep were higher in tumors compared to central gland (P < 0.005) and peripheral zone (P < 0.001). The initial area under the contrast concentration curve was higher in tumor than the peripheral zone (P < 0.001). The area under the receiver operating characteristic curve of the combined DWI and DCE parameters (0.78) was higher than its individual components (0.73 and 0.63, respectively) for discriminating low- and intermediate-to-high-risk tumors. The sIVIM model provided comparable results with fewer b-values and shorter image acquisition time. The combination of DWI and DCE measurements of MRI-visible index lesions improved the preoperative prostate cancer risk characterization compared to the individual parameters from either technique alone. 3 J. Magn. Reson. Imaging 2017;45:908-916.

Quantitative magnetic resonance imaging in the transgenic APC(Δ468) mouse model of hereditary colon cancer.

In this study, we investigated the use of high-resolution magnetic resonance imaging (MRI) methods for in vivo detection and quantitative characterization of colorectal tumors in the transgenic APC(Δ468) mouse model. High-resolution T(1)-weighted (T(1)W) images, T(2)-weighted (T(2)W) images, and dynamic contrast-enhanced (DCE) measurements were performed using a 7.0 T small-animal imaging system (N = 10). Individual tumors were identified on both T(1)W and T(2)W images. Twenty-eight tumors (2.8 ± 0.9 mm, mean ± SD) were detected with high-resolution MRI across a distance of roughly 3 cm from the rectum to the splenic flexure, whereas 29 tumors were found within corresponding colon tissue samples examined at gross necropsy in the same area. T(2) values were significantly different between tumor, skeletal muscle, and normal intestinal wall tissues (p < .05). For analysis of the vascular characteristics of colon tumor tissues using DCE measurements, the initial area under the curve (IAUC) for Gd contrast concentration curve (time) (C(Gd) [t]) was calculated with integration times of 60 and 120 seconds post-contrast infusion; two integration times were selected to capture both tracer wash-in and wash-out characteristics. IAUC measurements were significantly larger in tumor tissues compared to both normal intestinal wall and skeletal muscle tissues (p < .001). In vivo anatomic and quantitative MRI measurements were readily feasible in the transgenic APC(Δ468) mouse model. These noninvasive methods should improve experimental efficiencies during longitudinal survival studies that otherwise would require single-end-point necropsy measurements.

Dynamic contrast-enhanced magnetic resonance imaging in patients with pulmonary arterial hypertension.

Dynamic contrast-enhanced (DCE) time-resolved magnetic resonance (MR) imaging is a technique whereby the passage of an intravenous contrast bolus can be tracked through the pulmonary vascular system. The aim of this study was to investigate the prognostic significance of DCE-MR pulmonary blood transit times in patients with pulmonary arterial hypertension (PAH). Seventy-nine patients diagnosed with PAH underwent pulmonary DCE imaging at 1.5 T using a time-resolved three-dimensional spoiled gradient echo sequence. The prognostic significance of two DCE parameters, full width at half maximum (FWHM) of the first-pass clearance curve and pulmonary transit time (PTT), along with demographic and invasive catheter measurements, was evaluated by univariate and bivariate Cox proportional hazards regression and Kaplan-Meier analysis. DCE-MR transit times were most closely correlated with cardiac index (CI) and pulmonary vascular resistance index (PVRI) and were both found to be accurate for detecting reduced CI (FWHM area under the curve [AUC] at receiver operating characteristic analysis = 0.91 and PTT AUC = 0.92, respectively) and for detecting elevated PVRI (FWHM AUC = 0.88 and PTT AUC = 0.84, respectively). During the follow-up period, 25 patients died. Patients with longer measurements of FWHM (P = 0.0014) and PTT (P = 0.004) were associated with poor outcome at Kaplan-Meier analysis, and both parameters were strong predictors of adverse outcome from Cox proportional hazards analysis (P = 0.013 and 0.010, respectively). At bivariate analysis, DCE measurements predicted mortality independent of age, gender, and World Health Organization functional class; however, invasive hemodynamic indexes CI, PVRI, and DCE measurements were not independent of one another. In conclusion, DCE-MR transit times predict mortality in patients with PAH and are closely associated with clinical gold standards CI and PVRI.

A dedicated automated injection system for dynamic contrast‐enhanced MRI experiments in mice

To develop a reproducible small-animal dynamic contrast-enhanced (DCE) MRI set-up for mice through which volumes <100 μL can be accurately and safely injected and to test this set-up by means of DCE measurements in resting muscle and tumor tissue. The contrast agent (CA) injection system comprised 2 MR-compatible syringe pumps placed 50 cm from the 7T magnet bore where the fringe field is approximately 40 mT. Microbore tubing and T-connector, close to the injection site, minimized dead volume (<10 μL). For DCE-MRI measurements in 8 CB-17 SCID mice with 1500-2500 mm(3) large orthotopic neuroblastoma, a bolus of 10-fold-diluted Gd-DTPA CA solution (0.1 mmol/kg) was delivered (5 μL/s), followed by a 50-μL saline flush. Retro-orbital injections were given instead of tail vein injections, because the peripheral vasculature was reduced because of large tumor burden. The CA injection was successful in 19 of 24 experiments. Optical assessment showed minimal dispersion of ink-colored CA bolus. Mean (± SD) pharmacokinetic parameters retrieved from DCE-MRI examinations in resting muscle (K(trans) = 0.038 ± 0.025 min(-1), k(ep) = 0.66 ± 0.48 min(-1), v(e) = 0.060 ± 0.014, v(p) = 0.033 ± 0.021) and tumor (K(trans) = 0.082 ± 0.071 min(-1), k(ep) = 0.82 ± 0.80 min(-1), v(e) = 0.121 ± 0.075, v(p) = 0.093 ± 0.051) agreed with those reported previously. We successfully designed and implemented a DCE-MRI set-up system with short injection lines and low dead volume. The system can be used at any field strength with the syringe pumps placed at a sufficiently low fringe field (<40 mT).

Lower density of d2 dopamine receptors in the limbic system of alcohol — preferring rats

Prenatal alcohol exposure leads to impaired fetal growth, brain development, and stillbirth. Placental impairment likely contributes to these adverse outcomes, but the mechanisms and specific vasoactive effects of alcohol that links altered placental function to impaired fetal development remain areas of active research.Recently, we developed magnetic resonance imaging techniques in nonhuman primates to characterize placental blood oxygenation through measurements of T2* and perfusion using dynamic contrast-enhanced magnetic resonance imaging. The objective of this study was to evaluate the effects of first-trimester alcohol exposure on macaque placental function and to characterize fetal brain development in vivo.Timed-pregnant Rhesus macaques (n=12) were divided into 2 groups: control (n=6) and ethanol exposed (n=6). Animals were trained to self-administer orally either 1.5 g/kg/d of a 4% ethanol solution (equivalent to 6 drinks/d) or an isocaloric control fluid from preconception until gestational day 60 (term is G168). All animals underwent Doppler ultrasound scanning followed by magnetic resonance imaging that consisted of T2* and dynamic contrast-enhanced measurements. Doppler ultrasound scanning was used to measure uterine artery and umbilical vein velocimetry and diameter to calculate uterine artery volume blood flow and placental volume blood flow. After noninvasive imaging, animals underwent cesarean delivery for placenta collection and fetal necropsy at gestational day 110 (n=6) or 135 (n=6).Fetal weight and biparietal diameter were significantly smaller in ethanol-exposed animals compared with control animals at gestational day 110. By Doppler ultrasound scanning, placental volume blood flow was significantly lower (P=.04) at gestational day 110 in ethanol-exposed vs control animals. A significant reduction in placental blood flow was evident by dynamic contrast-enhanced magnetic resonance imaging. As we demonstrated recently, T2* values vary throughout the placenta and reveal gradients in blood deoxyhemoglobin concentration that range from highly oxygenated blood (long T2*) proximal to spiral arteries to highly deoxygenated blood (short T2*). Distributions of T2*throughout the placenta show significant global reduction in T2* (and hence high blood deoxyhemoglobin concentration) in ethanol-exposed vs control animals at gestational day 110 (P=.02). Fetal brain measurements indicated impaired growth and development at gestational day 110, but less so at gestational day 135 in ethanol-exposed vs control animals.Chronic first-trimester ethanol exposure significantly reduces placental perfusion and oxygen supply to the fetal vasculature later in pregnancy. These perturbations of placental function are associated with fetal growth impairments. However, differences between ethanol-exposed and control animals in placental function and fetal developmental outcomes were smaller at gestational day 135 than at gestational day 110. These findings are consistent with placental adaptation to early perturbations that allow for compensated placental function and maintenance of fetal growth.