Focal fat deposition at liver MRI with gadobenate dimeglumine and gadoxetic acid: Quantitative and qualitative analysis

Objective

To evaluate the image findings of focal fat deposition (FFD) in the liver on gadobenate dimeglumine (Gd-BOPTA)- and gadoxetic acid (Gd-EOB-DTPA)-enhanced MRI, particularly during the hepatobiliary phase (HBP), and the relationship between relative enhancement (RE) and fat signal fraction (FSF) of FFD.

Subjects and Methods

Twenty-one patients with 27 FFDs (mean diameter, 21.9 mm), which showed low signal intensity on opposed-phase compared with in-phase MRI, were retrospectively evaluated. RE of the liver (RE_liver) and FFD (RE_FFD) and liver-to-lesion contrast-to-noise ratio (CNR) of FFD were measured on dynamic phases and HBP images with fat-saturated in-phase gradient-echo sequence. The FSF of each FFD was measured on in- and opposed-phase dual gradient-echo images. We qualitatively analyzed imaging findings of FFDs, including signal intensity, shape, margin, and homogeneity on HBP images, and enhancement pattern during dynamic phases. The correlations between RE_FFD and FSF and between CNR and FSF on HBP images were evaluated using Pearson’s correlation tests and a simple linear regression model.

Results

There were no significant differences between RE_FFD and RE_liver in dynamic phases and HBP, regardless of contrast agents (p ≥ 0.075). On HBP images, CNR (p = 0.008) but not RE_FFD (p = 0.122) was significantly correlated with FSF of FFDs (mean FSF, 19%). On HBP images, 21 of the 27 (77.8%) FFDs were hypointense, and 17 (63%) were homogeneous. Of the 21 hypointense FFDs, 12 (57.1%) had an ovoid shape and 11 (52.4%) were well margined. Although the 27 FFDs showed various enhancement patterns, 17 (63%) showed no enhancement.

Conclusion

Most FFDs appeared as hypointense lesions on Gd-BOPTA- and Gd-EOB-DTPA-enhanced MRI during HBP, with various enhancement patterns during dynamic contrast-enhanced phases. RE_FFD on HBP images was not significantly correlated with FSF of low grade FFDs.     

Objective evaluation of acute adverse events and image quality of gadolinium-based contrast agents (gadobutrol and gadobenate dimeglumine) by blinded evaluation. Pilot study

Purpose

The purpose was to objectively evaluate a recently FDA-approved gadolinium-based contrast agent (GBCA) in comparison to our standard GBCA for acute adverse events and image quality by blinded evaluation.

Methods

Evaluation was made of a recently FDA-approved GBCA, gadobutrol (Gadavist; Bayer), in comparison to our standard GBCA, gadobenate dimeglumine (MultiHance; Bracco), in an IRB- and HIPAA-compliant study. Both the imaging technologist and patient were not aware of the brand of the GBCA used. A total of 59 magnetic resonance studies were evaluated (59 patients, 31 men, 28 women, age range of 5–85 years, mean age of 52 years). Twenty-nine studies were performed with gadobutrol (22 abdominal and 7 brain studies), and 30 studies were performed with gadobenate dimeglumine (22 abdominal and 8 brain studies). Assessment was made of acute adverse events focusing on objective observations of vomiting, hives, and moderate and severe reactions. Adequacy of enhancement was rated as poor, fair and good by one of two experienced radiologists who were blinded to the type of agent evaluated.

Results

No patient experienced acute adverse events with either agent. The target minor adverse events of vomiting or hives, and moderate and severe reactions were not observed in any patient. Adequacy of enhancement was rated as good for both agents in all patients.

Conclusions

Objective, blinded evaluation is feasible and readily performable for the evaluation of GBCAs. This proof-of-concept study showed that both GBCAs evaluated exhibited consistent good image quality and no noteworthy adverse events.     

The gadolinium complexes with polyoxometalates as potential MRI contrast agents

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

Potential clinical factors affecting hepatobiliary enhancement at Gd-EOB-DTPA-enhanced MR imaging

Objective

The objective was to clarify the clinical factors that might affect the degree of hepatic parenchymal enhancement at gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance (MR) imaging.

Materials and Methods

A total of 84 patients with (n=63) and without chronic liver disease (n=21) underwent Gd-EOB-DTPA-enhanced MR imaging. Contrast-enhanced MR images of hepatobiliary phase (HP) were obtained at 20 min after Gd-EOB-DTPA administration. The relative enhancement (RE) of liver parenchyma at 20 min HP was calculated from region of interest measurements at each patient. Then, these results were correlated with various clinical parameters using Pearson correlation coefficient or Spearman rank correlation coefficient. Furthermore, the predictor of the degree of hepatic parenchymal enhancement was determined using multiple regression analysis.

Results

The presence or absence of chronic liver disease (P=.002), ascites (P=.005) and splenomegaly (P=.027), and the values of prothrombin activity (P=.008), total bilirubin (T-Bil) (P=.001), albumin (P=.001), aspartate aminotransferase (AST) (P=.002) and cholinesterase (P=.007) were significantly correlated with the RE of liver parenchyma at 20 min HP. Among these parameters, increases of T-Bil (P=.011 to .028) and AST (P=.018 to .049) were predictors of decreased hepatic parenchymal enhancement.

Conclusions

Hepatic parenchymal enhancement of Gd-EOB-DTPA was affected by various clinical parameters. Impaired hepatobiliary enhancement may be predicted by routine biochemical tests, such as T-Bil and AST.     

The use of Gd DTPA as a perfusion agent and marker of blood-brain barrier disruption

To provide contrast enhancement in magnetic resonance imaging, a new class of compounds has been developed, the paramagnetic metal ion chelates. Gadolinium (Gd) DTPA, a prototype of this class, shows a sufficiently high in vivo stability and low toxicity for use in initial clinical trials. This type of agent, designed for rapid clearance by glomerular filtration, allows the assessment on MRI of renal function, alterations in tissue perfusion, myocardial ischemia, and perhaps most significantly disruption of the blood-brain barrier (BBB). Research at Vanderbilt has demonstrated these applications, with particular emphasis in three areas. Tissue perfusion changes, such as those produced by ligation of the arterial blood supply to portions of the spleen and kidney, cannot easily be detected on unenhanced MRI. These acute tissue infarcts can be readily identified following the administration of Gd DTPA. The question of field strength dependence of Gd DTPA has been addressed by experimentation at 0.15, 0.5, and 1.5 tesla. Furthermore, the ability to detect an alteration of the BBB, when present without associated edema, has been demonstrated with the application of control enhancement. The use of contrast agents in MRI will enhance both the sensitivity and specificity of magnetic resonance imaging.     

Gd complexes of diethylenetriaminepentaacetic acid conjugates of low-molecular-weight chitosan oligosaccharide as a new liver-specific MRI contrast agent

This study was to describe the synthesis of complexes of gadolinium diethylenetriaminepentaacetic acid conjugates of low-molecular-weight chitosan oligosaccharide Gd-DTPA-CSn (n = 6, 8, 11) as a new class of contrast agent as well as its magnetic property in a pilot magnetic resonance imaging. The efficacy of the contrast agent was assessed by measuring the longitudinal relaxivity (r₁), FLASH imaging in phantoms in vitro and signal intensity in vivo of the rat abdominal axial imaging. The r₁ of Gd-DTPA-CS₁₁ was up to 11.65 mM^− 1·s^− 1, which was 3 times higher than that of the analogous MRI contrast agent Gd-DTPA in commercial use. In vivo MR images of rat obtained with Gd-DTPA-CS₁₁ showed strong signal enhancement in liver and the vessels of the liver parenchyma during the extended period of time. The present study suggests that the new synthesized gadolinium complexes can be used as a new class of practical liver-specific MRI contrast agent because of its superior performance compared with Gd-DTPA.     

Noncontrast MRI with diffusion-weighted imaging as the sole imaging modality for detecting liver malignancy in patients with high risk for hepatocellular carcinoma

Purpose

To compare the diagnostic performance of the noncontrast MRI including DWI to the standard MRI for detecting hepatic malignancies in patients with chronic liver disease.

Materials and methods

We included 135 patients with 136 histologically-confirmed hepatocellular carcinomas (HCCs), 12 cholangiocarcinomas, and 34 benign lesions (≤ 2.0 cm), and 22 patients with cirrhosis but no focal liver lesion who underwent 3.0 T liver MRI. Noncontrast MRI set (T1- and T2-weighted images and DWI) and standard MRI set (gadoxetic acid-enhanced and noncontrast MRI) were analyzed independently by three observers to detect liver malignancies using receiver operating characteristic analysis.

Results

The Az value of the noncontrast MRI (mean, 0.906) was not inferior to that of the combined MRI (mean, 0.924) for detecting malignancies by all observers (P > 0.05). For each observer, no significant difference was found in the sensitivity and specificity between the two MRI sets for detecting liver malignancies and distinguishing them from benign lesions (P > 0.05), whereas negative predictive value was higher with the combined MRI than with the noncontrast MRI (P = 0.0001). When using pooled data, the sensitivity of the combined MRI (mean 94.8%) was higher than that of the noncontrast MRI (mean, 91.7%) (P = 0.001), whereas specificity was equivalent (78.6% vs 77.5%).

Conclusion

Noncontrast MRI including DWI showed reasonable performance compared to the combined gadoxetic acid-enhanced and noncontrast MRI set for detecting HCC and cholangiocarcinoma and differentiating them from benign lesions in patients with chronic liver disease.     

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

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

Superparamagnetic iron oxide nanoparticles as a liver MRI contrast agent: Contribution of microencapsulation to improved biodistribution

We have developed a new method of synthetizing superparamagnetic iron oxide nanoparticles, consisting in the modifications of Molday's method, which ensures high relaxivity (2.4 10⁵ s⁻¹·M⁻¹·L), good chemical stability, singular biodistribution and a considerable safety margin. The ED (Efficace Dose) to LD50 ratio is instead of for Gd-DTPA. In order to develop a magnetite-delivery system to the liver we have incorporated the nanoparticles into biodegradable synthetic microcapsules. Encapsulated ⁵⁹Fe oxide nanoparticles are injected into rats; in these conditions the sequestration is 9-fold greater in liver and 6 and 5 times lower in blood and carcase, respectively. This modification of the biodistribution enables the use of magnetite containing microcapsules at only 0.3 mg/kg iron to obtain an improved contrast in liver.     

Optimal techniques for magnetic resonance imaging of the liver using a respiratory navigator-gated three-dimensional spoiled gradient-recalled echo sequence

Purpose

To optimize the navigator-gating technique for the acquisition of high-quality three-dimensional spoiled gradient-recalled echo (3D SPGR) images of the liver during free breathing.

Materials and methods

Ten healthy volunteers underwent 3D SPGR magnetic resonance imaging of the liver using a conventional navigator-gated 3D SPGR (cNAV-3D-SPGR) sequence or an enhanced navigator-gated 3D SPGR (eNAV-3D-SPGR) sequence. No exogenous contrast agent was used. A 20-ms wait period was inserted between the 3D SPGR acquisition component and navigator component of the eNAV-3D-SPGR sequence to allow T1 recovery. Visual evaluation and calculation of the signal-to-noise ratio were performed to compare image quality between the imaging techniques.

Result

The eNAV-3D-SPGR sequence provided better noise properties than the cNAV-3D-SPGR sequence visually and quantitatively. Navigator gating with an acceptance window of 2 mm effectively inhibited respiratory motion artifacts. The widening of the window to 6 mm shortened the acquisition time but increased motion artifacts, resulting in degradation of overall image quality. Neither slice tracking nor incorporation of short breath holding successfully compensated for the widening of the window.

Conclusion

The eNAV-3D-SPGR sequence with an acceptance window of 2 mm provides high-quality 3D SPGR images of the liver.     

HCC-to-liver contrast on arterial-dominant phase images of EOB-enhanced MRI: comparison with dynamic CT

The purpose of this study was to assess the efficacy of arterial-dominant phase images of gadolinium–ethoxybenzyl–diethylenetriamine pentaacetic acid (EOB)-enhanced magnetic resonance imaging (MRI) for evaluation of arterial blood supply in hepatocellular carcinoma (HCC) in comparison with that of multiphasic dynamic computed tomography (CT). This study comprised 30 patients (22 men and 8 women, mean age: 68.0 years) with 40 pathologically proven HCCs (well differentiated: 3, moderately differentiated: 30, poorly differentiated: 7, mean diameter: 45.1 mm), all of whom underwent EOB-enhanced MRI and dynamic CT preoperative assessment. Regions of interest were placed over HCCs and the adjacent normal liver, and signal intensities or CT values were measured by two experienced abdominal radiologists on the arterial-dominant phase images of EOB-enhanced MRI and dynamic CT images. HCC-to-liver contrasts [Michelson's contrast: C_M=(S_HCC− S_Liver)/(S_HCC+ S_Liver)] were calculated and compared among the modalities. HCC-to-liver contrasts were also visually scored on a 5-point scale and compared. The mean C_M and visual score for dynamic CT were significantly higher than those for EOB-enhanced MRI. Good agreements were obtained among the two observers. Dynamic CT is a more suitable modality than EOB-enhanced MRI for evaluation of arterial blood supply in HCC. This should be taken into account for diagnosis and management of HCC.     

Hepatic parenchymal enhancement at Gd-EOB-DTPA-enhanced MR imaging: correlation with morphological grading of severity in cirrhosis and chronic hepatitis

The aim was to clarify whether enhancement effects of the liver parenchyma in the hepatobiliary phase (HP) of gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced MR imaging were correlated with the morphological grading of the severity in cirrhosis. A total of 62 patients with chronic hepatitis or cirrhosis underwent Gd-EOB-DTPA-enhanced MR imaging. Relative enhancement (RE) of liver parenchyma was calculated from signal intensity (SI) measurements obtained at precontrast images (SIpre) and 20-min postcontrast HP images (SIpost) as: (SIpost-SIpre)/SIpre. Morphological MR grades of severity in cirrhosis were divided into four groups. Then, RE of liver parenchyma and morphologic MR grading were correlated. Regarding the morphologic severity of cirrhosis, the numbers of patients with MR grade 1, 2, 3 and 4 were 14 (23%), 7 (11%), 28 (45%) and 13 (21%), respectively. The mean REs of liver parenchyma in each group of MR morphologic grade 1, 2, 3 and 4 were 0.71±0.21, 0.62±0.16, 0.70±0.22 and 0.77±0.18, respectively. There was no significant correlation between the MR grading of morphologic severity and the RE of liver parenchyma at 20-min HP. Hepatic parenchymal enhancement in the HP of Gd-EOB-DTPA-enhanced MR imaging did not necessarily decrease according to the severity of morphologic changes in cirrhosis. This fact may suggest that the hepatic uptake of Gd-EOB-DTPA depends on the preserved hepatocytes function rather than the severity of morphologic changes in cirrhosis.     

Comparison of gadolinium chelates with manganese-DPDP for liver lesion detection and characterization: Preliminary results

Nonspecific extracellular gadolinium chelate (NEGd) was prospectively compared with manganese (Mn)-DPDP (Mn) for the detection and characterization of focal liver lesions of various histology. Seventeen patients with known or suspected focal liver lesions underwent NEGd and Mn-enhanced studies at 1.5 T. Study findings were correlated with histology (five patients), computed tomography (CT) examinations (17 patients), and 4- to 13-month imaging follow-up by CT and/or MR (five patients). NEGd studies were performed as serial postcontrast spoiled gradient echo (SGE) sequences, and Mn studies were performed as SGE sequences 15 and 30 min postcontrast and T₁-weighted, fat-suppressed spin echo at 16 min. NEGd and Mn images were prospectively interpreted in a separate blinded fashion. Lesion detection and characterization were determined. NEGd and Mn-enhanced images demonstrated 61 and 49 lesions, respectively (p = .1, NS). A total of 60 and 33 lesions were characterized on NEGd and Mn images, respectively, which was significantly different (p = .008). No differences were observed for the detection and characterization of liver metastases; whereas there was a trend for superior detection and characterization for hepatocellular carcinoma with NEGA.     

Correlation between serum ferritin levels and liver iron concentration determined by MR imaging: impact of hematologic disease and inflammation

Liver iron concentration was determined in 28 patients by magnetic resonance imaging using the method of Gandon et al. (Non-invasive assessment of hepatic iron stores by MRI. Lancet 2004;363:357-362). The result showed a significant correlation with blood plasma ferritin content (Spearman's r=.66; P<.001) and a slightly improving correlation coefficient when limited to those patients not known to have inflammation (r=.82; n=17; P<.001). Zooming in on patients with hematologic disease also had a beneficial effect on the correlation between liver iron content and plasma ferritin level (r=.79; n=13; P=.001). It is concluded that in patients without inflammation and in patients with hematologic disease, the content of ferritin in blood is a better predictor of liver iron content than in other patient categories.     

Longitudinal magnetic resonance imaging of spinal cord injury in mouse: changes in signal patterns associated with the inflammatory response

Contusion-type spinal cord injury (SCI) in mice was followed longitudinally using in vivo magnetic resonance (MR) imaging along with neurobehavioral tests performed on postinjury Days 1, 7, 14 and 28. Magnetic resonance images were acquired from seven injured wild-type mice using a 9.4-T scanner and presented in sagittal and axial views to reflect the current state of the injured cord neuropathology on each day. The data were analyzed individually to gain more insights on the neuroinflammatory response unique to the mouse, to characterize the spatiotemporal evolution of the lesion and to quantify the changes in lesion volume and length with time. The MR intensity patterns on Day 1 showed acute injuries as focal in one group of three mice and as diffuse in the remaining group of four mice. The focal injuries appeared as a region of hypointensity with well-defined boundaries. These injuries first enlarged on Day 7, but then shrunk slightly by Days 14 and 28. In contrast, the diffuse injuries were initially obscure on Day 1, mainly because of loss of contrast between gray and white matters. On Day 7, lesions expanded asymptotically in both rostral and caudal directions with respect to the epicenter, and maintained its size on Days 14 and 28. Previous studies based on postmortem histological analysis have reported lesions behaving more like in the focal group. However, this new injury with diffuse characteristics may have important implications for SCI research carried out with mice. Unique experiments on genetically engineered mice with altered neuroinflammatory response should help clarify the origin of these differences in the lesion formation.     

The oral administration of MnCl2: A potential alternative to IV injection for tissue contrast enhancement in magnetic resonance imaging

Mn⁺² (as MnCl₂) was administered to rabbits intravenously and orally (a route of administration which based upon our previous experiments in rats⁷ promises to give selective hepatobiliary enhancement with less systemic toxicity). Nuclear magnetic relaxation dispersion or T₁ (NMRD) was performed on selected tissues (heart, liver, kidney, serum, and bile) in both animal groups to examine possible qualitative and semiquantitative differences in T₁ relaxation at equivalent sacrifice times. One animal was given an oral dose of MnCl₂ (620 micromoles/kg) and imaged sequentially (T₁ weighted sequence, .12T) for 30 minutes. The NMRD curves for organ tissues show an increase in relaxation efficacy in the 10–20MHz range characteristic of Mn-macromolecular complexes and are similar irrespective of the route of administration. The lack of increased relaxation enhancement for bile in this frequency range reflects cleavage of this complex upon excretion. Decreased overall relaxation in the liver is observed when oral Mn⁺² is compared to IV Mn⁺² due to the small fraction of administered dose that is absorbed. However, the images document a significant increase in the intensity of liver signal after the oral dose. We suspect this dose may ultimately be adjusted downward to give selective hepatobiliary effects.     

Intravoxel incoherent motion imaging of the kidney: alterations in diffusion and perfusion in patients with renal dysfunction

Purpose

To investigate the relationship between estimated glomerular filtration rate (eGFR) and parameters calculated using intravoxel incoherent motion (IVIM) imaging of the kidneys.

Materials and Methods

We studied 365 patients, divided into 4 groups based on eGFR levels (mL/min/1.73 m²): group 1, eGFR ≥ 80(n = 80); group 2, eGFR 60–80 (n = 156); group 3, eGFR 30–60 (n = 114); and group 4 ,eGFR < 30 (n = 15). IVIM imaging was used to acquire diffusion-weighted images at 12 b values. The diffusion coefficient of pure molecular diffusion (D), the diffusion coefficient of microcirculation or perfusion (D*), and perfusion fraction (f) were compared among the groups using group 1 as control.

Results

In the renal cortex, D* values were significantly lower in groups 2, 3, and 4 than in group 1. The D value of renal cortex was significantly low in only group 3. In the renal medulla, the D* and D values were significantly lower only in groups 2 and 3, respectively.

Conclusion

As renal dysfunction progresses, renal perfusion might be reduced earlier and affected more than molecular diffusion in the renal cortex. These changes are effectively detected by IVIM MR imaging.     

Preparation and in vitro evaluation of poly(D,L-lactide-co-glycolide) air-filled nanocapsules as a contrast agent for ultrasound imaging

The aim of this study was to prepare air-filled nanocapsules intended ultrasound contrast agents (UCAs) with a biodegradable polymeric shell composed of poly(d,l-lactide-co-glycolide) (PLGA). Because of their size, current commercial UCAs are not capable of penetrating the irregular vasculature that feeds growing tumors. The new generation of UCAs should be designed on the nanoscale to enhance tumor detection, in addition, the polymeric shell in contrast with monomolecular stabilized UCAs improves the mechanical properties against ultrasound pressure and lack of stability. The preparation method of air-filled nanocapsules was based on a modification of the double-emulsion solvent evaporation technique. Air-filled nanocapsules with a mean diameter of 370 ± 96 nm were obtained. Electronic microscopies revealed spherical-shaped particles with smooth surfaces and a capsular morphology, with a shell thickness of ∼50 nm. Air-filled nanocapsules showed echogenic power in vitro, providing an enhancement of up to 15 dB at a concentration of 0.045 mg/mL at a frequency of 10 MHz. Loss of signal for air-filled nanocapsules was 2 dB after 30 min, suggesting high stability. The prepared contrast agent in this work has the potential to be used in ultrasound imaging.     

Novel mineral contrast agent for magnetic resonance studies of bone implants grown on a chick chorioallantoic membrane

Magnetic resonance imaging (MRI) studies of tissue engineered constructs prior to implantation clearly demonstrate the utility of the MRI technique for studying the bone formation process. To test the utility of our MRI protocols for explant studies, we present a novel test platform in which osteoblast-seeded scaffolds were implanted on the chorioallantoic membrane of a chick embryo. Scaffolds from the following experimental groups were examined by high-resolution MRI: (a) cell-seeded implanted scaffolds (CIM), (b) unseeded implanted scaffolds (UCIM), (c) cell-seeded scaffolds in static culture (CIV) and (d) unseeded scaffolds in static culture (UCIV). The reduction in water proton transverse relaxation times and the concomitant increase in water proton magnetization transfer ratios for CIM and CIV scaffolds, compared to UCIV scaffolds, were consistent with the formation of a bone-like tissue within the polymer scaffold, which was confirmed by immunohistochemistry and fluorescence microscopy. However, the presence of angiogenic vessels and fibrotic adhesions around UCIM scaffolds can confound MRI findings of bone deposition. Consequently, to improve the specificity of the MRI technique for detecting mineralized deposits within explanted tissue engineered bone constructs, we introduce a novel contrast agent that uses alendronate to target a Food and Drug Administration-approved MRI contrast agent (Gd-DOTA) to bone mineral. Our contrast agent termed GdALN was used to uniquely identify mineralized deposits in representative samples from our four experimental groups. After GdALN treatment, both CIM and CIV scaffolds, containing mineralized deposits, showed marked signal enhancement on longitudinal relaxation time-weighted (T1W) images compared to UCIV scaffolds. Relative to UCIV scaffolds, some enhancement was observed in T1W images of GdALN-treated UCIM scaffolds, subjacent to the dark adhesions at the scaffold surface, possibly from dystrophic mineral formed in the fibrotic adhesions. Notably, residual dark areas on T1W images of CIM and UCIM scaffolds were attributable to blood inside infiltrating vessels. In summary, we present the efficacy of GdALN for sensitizing the MRI technique to the deposition of mineralized deposits in explanted polymeric scaffolds.     

Diffusion-weighted magnetic resonance imaging to evaluate microvascular density after transarterial embolization ablation in a rabbit VX2 liver tumor model

Objective

To evaluate the correlation between findings from diffusion weighted imaging (DWI) and microvascular density (MVD) measurements in VX2 liver tumors after transarterial embolization ablation (TEA).

Materials and Methods

Eighteen New Zealand white rabbits were used in this study. VX2 tumor cells were implanted in livers by percutaneous puncture under computed tomography (CT) guidance. Two weeks later, all rabbits underwent conventional magnetic resonance imaging (MRI) (T1 and T2 imaging), DWI, (b = 100, 600, and 1000 s/mm²) and TEA. MRI was performed again1 week after TEA. Liver tissue was then harvested and processed for hematoxylin and eosin (H&E) staining and immunohistochemical staining for CD31to determine MVD.

Results

VX2 liver tumors were successfully established in all 18 rabbits. Optimal contrast was achieved with a b value of 600 s/mm².The maximum pre-operative apparent diffusion coefficient (ADC)_difference value was 0.28 × 10^− 3 ± 0.10 × 10^− 3 mm²/s, and was significantly different (P < 0.001) from the maximum postoperative ADC_difference value of 0.47 × 10^− 3 ± 0.10 × 10^− 3 mm²/s. However, the mean ADC value for the entire tumor was not significantly correlated with MVD (r = 0.221, P = 0.379), nor was the ADC value for the regions of viable tumor (r = − 0.044, P = 0.862). However, the maximum postoperative ADC_difference value was positively correlated with MVD(r = 0.606, F = 12.247, P = 0.003).

Conclusion

DWI is effective to evaluate the therapeutic efficacy of TEA. The maximum ADC_difference offers a promising new method to noninvasively assess tumor angiogenesis.