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Do different injection rates of Gd-EOB-DTPA affect image quality and enhancement of liver parenchyma? An evaluation of cirrhotic patients at 1.5 and 3.0T MRI

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UNIVERSITÀ DI PISA

Dipartimento di Ricerca Traslazionale e delle Nuove Tecnologie in

Medicina e Chirurgia

Scuola di Specializzazione in Radiodiagnostica

Direttore: Prof. Carlo Bartolozzi

TESI DI SPECIALIZZAZIONE

Do different injection rates of Gd-EOB-DTPA affect image quality

and enhancement of liver parenchyma? An evaluation of cirrhotic

patients at 1.5 and 3.0 T MRI

Relatore:

Chiar.mo Prof. Carlo Bartolozzi

Candidata:

Dr.ssa Sara Galeotti

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INDEX

ABSTRACT --- 2

INTRODUCTION --- 4

MATERIALS AND METHODS --- 6

RESULTS --- 12

DISCUSSION --- 14

CONCLUSION --- 19

TABLES --- 20

IMAGES --- 24

REFERENCES --- 29

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ABSTRACT

Objectives: To determine whether a fast injection rate (3mL/s) of Gd-EOB-DTPA affects livers Enhancement Ratios (ERs), Signal to Noise Ratio (SNR), and MR image quality, in comparison to a slow injection rate (1.5 mL/s), in cirrhotic patients submitted to either 1.5T or 3.0T MRI.

Materials and methods: We retrospectively reviewed the records of cirrhotic patients (Child A and Child B) submitted to Gd-EOB-DTPA enhanced MRI study of the liver between September 2010 and September 2013 at our institution.

Contrast administration was obtained by means of an automatic injector; in all studies, two arterial phases (early arterial and parenchymal arterial phases) were acquired, by means of a pre-definite, fixed scan delay method.

For each arterial phase, ERs of liver parenchymas and abdominal aortic lumen, and SNR were calculated. A qualitative analysis of Gibbs artifacts on both arterial phases was also performed.

Results: Out of 435 cirrhotic patients submitted to MR studies, 249 were considered eligible for study inclusion. On the basis of magnetic field strength (1.5T vs 3T) and contrast injection flow rate (1.5ml/sec vs 3ml/sec), patients were divided into four groups: Group I: 77 patients (1.5T and 1.5ml/s); Group II: 89 patients (1.5T and 3mL/s); Group III: 34 patients (3.0T and 1.5mL/s); Group IV: 49 patients (3.0T and 3mL/s).

Contrast injection rate resulted not to influence ERs of liver parenchymas on early arterial nor on parenchymal arterial phases (p 0.9573 and p 0.0308 respectively), nor

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ERs of aortic lumens on both arterial phases, nor ERs of other target structures, nor SNR of liver parenchymas on both arterial phase, nor the incidence of artifacts.

Magnetic field strength instead affects SNR of liver parenchymas on both arterial phases.

Conclusions: Our results suggest that contrast injection rate does not influence ERs of liver parenchymas on arterial phases, independently from magnetic field strength. Dedicated and optimized dynamic sequences might limit artifacts, independently from contrast injection flow rate.

Keywords: LAVA; Enhancement Ratio; Liver; High Field dynamic MR; Gadoxetic Acid

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INTRODUCTION

Gadolinium ethoxybenzyl diethylenetriaminepentaacetic acid (Gd-EOB-DTPA,

Primovist; Bayer Schering Parma, Berlin, Germany) is a fairly new liver-specific contrast agent, applied worldwide for dynamic and hepatobiliary study of the liver. Several studies have demonstrated that Gd-EOB-DTPA allows a reliable, dynamic, vascular study of the liver parenchyma, overlaying that obtained by means of nonspecific extracellular Gd-chelates, as well as the evaluation of residual hepatocyte function [1-2-3-4].

Moreover, because of the strong relaxivity of the molecule within human plasma, preclinical studies have assessed the proper dose of Gd-EOB-DTPA as 0.025 mmol/kg/patient body weight, equivalent to one quarter of the gadolinium dose administered for all other MRI contrasts [5].

Despite in clinical use since some years, actually a standardized protocol of acquisition of dynamic Gd-EOB-DTPA MR study has not been endorsed [6-7].

Particularly, many studies have been conducted in order to assess the best technical approach to obtain a proper arterial phase, still considered as the most important clue for characterizing a focal liver lesion [8].

Several factors might affect, in MR studies, a good technical performance of the dynamic evaluation and then, the diagnostic value of the examination. Regarding Gd-EOB-DTPA MR studies, of notice, optimal delayed time setting of arterial phase as well as contrast agent injection flow rate represent two main critical points [9].

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2ml/sec) flow injection of Gd-EOB-DTPA had been considered as critical, because of the supposed high incidence of artifacts (Gibbs phenomenon), especially on arterial phase, due to the possible abrupt break of the k space filling [10-17]. These considerations have led to support some quite established aknowledgements in contrast agent administration, such as the adoption of low injection rates (0.7-1ml/sec) as well as the application of diluition methods, associated to high flow rates injection (3ml/sec) [11].

Anyway, a fast injection of contrast agent permits its faster arrival within early enhancing tissues, resulting in a complete distribution at the time of scanning arterial phase, so emphasizing the signal intensity of structures characterized by “early wash-in”.

Regarding the optimization of arterial phase acquisition, actually most frequent applied protocols are represented by the “fixed scan delay” acquisition (consisting in acquiring one arterial phase at a fixed, predefined time), or by the “test injection method” (consisting in the acquisition of the arterial phase after the aortic peak enhancement) [12].

Because of the small amount of contrast medium dose, the fixed scan delay acquisition has resulted to be affected by a number of variables, such as patient cardiac output or metabolic status, that frequently leading to a suboptimal detection of hepatic parenchyma enhancement, especially if acquiring one single arterial phase

[13], and so limiting the diagnostic performance of MR examination. On the contrary, test injection method, even if better matching the time of peak enhancement in

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arterial phase, shows the limitation of the possible effects of the test bolus dose of contrast (0.5-1ml), administered before dynamic study, that might affect the signal intensity (SI) and contrast-to noise ratio (CNR) of the parenchymas and so the real enhancement of evaluated structures [12].

Independently from applied method, many technical parameters can be formulated for appropriate protocols in order to avoid artifacts and to obtain a quali-quantitative optimal arterial phase, i.e all parameters that can lead to short scanning time, by acquiring two subsequent arterial phase, selecting square matrix.

Aim of our study was to determine whether a fast injection rate (3mL/s) of Gd-EOB-DTPA affects livers enhancement ratios (ERs), signal to noise ratio (SNR), and MR image quality, in comparison to a slow injection rate (1.5 mL/s), in cirrhotic patients submitted to either 1.5T or 3.0T MRI.

MATERIALS AND METHODS

This was an Italian, single-centre, retrospective study. Study protocol was approved by institutional review board according to current Italian law on observational studies.

We retrospectively reviewed the records of cirrhotic patients (Child A and Child B) submitted to Gd-EOB-DTPA enhanced MRI study of the liver between September 2010 and September 2013 at our institution.

Exclusion criteria were the following: previous orthothopic liver transplantation; Child C (because of ascitis); previous (<1 year) major cardiovascular injury or known

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history of cardiac arithmia; abnormal renal function; distant tumoral involvement; intrahepatic tumoral involvement (primitive or persistence after treatment) outside Milans’ criteria; morphological alteration of the intrahepatic or extra hepatic biliary tree; thrombosis of the subsegmentary, segmentary or intrahepatic main portal branches nor of the main portal trunk, nor of the splenic vein; the presence of intrahepatic artero-venous fistula or portal cavernomatosis, or the presence of thoraco-abdominal aortic aneurism.

MR Imaging Protocol

Dynamic MRI was performed after administration of Gd-EOB-DTPA (Primovist; Bayer-Schering, Berlin, Germany), using a fat suppressed, volumetric, interpolated breath-hold, spoiled gradient- recalled-echo T1- weighted sequence acquired in the axial plane.

In patients studied at 1.5T MRI, a LAVA-XV (Liver Acquisition with Volume Acceleration - eXtended Volume) sequence, was applied, while in patients studied at 3T MRI, a LAVA Flex (Liver Acquisition with Volume Acceleration) sequence was performed.

Technical parameters of the pulse sequences of both systems (TR-Repetition Time; TE-Echo Time; NEX, Flip Angle, Matrix, slice thickness, phase FOV, enconding phase) are reported on Table 1.

Pre-saturation pulses were applied above and below the imaging volume to reduce flow artifacts from vessels.

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In all examinations, a self-calibrated parallel imaging method (ARC-Auto-calibrating Reconstruction for Cartesian sampling) was applied, in order to reduce motion artifacts; moreover, in LAVA-XV sequence a ZIP512x512 and ZIPx2 (Zero Filling Interpolation Processing) were applied, while in LAVA-FleX sequence a ZIPx2 was applied.

After the acquisition of the unenhanced MR sequences, Gd-EOB-DTPA at a dose of 0.025 mmol/kg body weight was automatically injected (1.5T MRI: Medrad Spectris Solaris EP- Bayer; 3T MRI: EZM EMPOWER RM ACIS- Bracco) into a antecubital vein through a 22-gauge catheter at a flow rate of 1.5mL/s and 3mL/s, followed by a 20mL saline chaser, at the same injection rate.

Enhanced MR images were obtained in all patients by using a “modified” fixed scan delay: the acquisition of early arterial phase was started 15 seconds after the start of the contrast injection, while the acquisition of arterial parenchymal phase was started immediately at the end of the early arterial phase (ranging time 30-40 sec after the contrast medium injection). Portal venous phase and late dynamic phase were acquired at a fixed time of 70 sec and 180 sec after the start of contrast medium injection.

Image Analysis

Quantitative assessment

Dynamic MR studies were reviewed and evaluated at a dedicated consolle (Advantage Windows 4.5, GE Medical System, Milwaukee USA), by recalling images from PACS (Picture Archiving and Communications System).

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Two radiologists with more than 5 years of experience in liver MRI drew a circular, standard Regions of Interest (ROIs) by consensus, in order to measure the Signal Intensities (SI) of predefined structures on the selected images. The means and standard deviations (SDs) of each target were recorded.

Target structures were: liver parenchyma on unenhanced, early arterial, parenchymal arterial and portal venous phase; abdominal aortic lumen at the level of the thoraco-abdominal passage, of the emergency of the coeliack trunk and at the emergency of renal arteries on early arterial and on parenchymal arterial phase; the portal vein at the level of its extra-hepatic tract on the portal venous phase and the splenic parenchyma on the portal venous phase.

ROIs positioned in the liver parenchyma, spleen and in the aortic lumen had a predefinite area of 150mm2; ROIs’ areas in the portal vein were as large as possible, on the basis of vessel caliber.

Regarding the liver parenchyma, ROIs were drawn in predefinite locations (periphery of the VII, VIII, IV and III segment), at the level of the bifurcation of the portal vein. In order to perform a correct and reproducible measurement for each case, we did apply an automatic positioning of the ROIs of the selected areas of each parenchyma, simultaneously in the four different phases of acquisition (unenhanced, early arterial, parenchymal arterial, venous phase) (Image 1 and 2.1-2.2).

When the ROI was set, great care was taken to exclude the large vessels, to minimize any errors in SI measurements from macroscopic flow. The average values of SI of

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liver parenchyma were then calculated for each acquisition phase, to be used for data analysis.

From the measured SI, we did evaluate the enhancement ratio (ER) of the livers on early arterial and parenchymal arterial phases, by the following: (SIpost-SIpre)/SIpre, where SIpost is the SI after the administration of contrast material and SIpre is the SI before the administration of contrast material [14].

ERs of aortic lumens, and of other target structures were calculated with the same method.

A quantitative analysis of Signal-to-Noise Ratio (SNR) of livers on early arterial and parenchymal arterial phases for each MR study, was calculated as follows: SNR: 1⁄4

SI (target structure on the selected phase)/ Noise (SD of background on the unenhanced acquisition) [15].

Image noise was measured as SD of a ROI outside the body volume along the phase-encoding direction on baseline acquisition: particularly, in order to avoid in all cases the aorta artefact, ROI were positioned at a distance of 1.5cm, on the right side of the image [16] (Image 3).

Qualitative analysis

All MR images were also qualitatively interpreted, in consensus by two experienced abdominal radiologists with 8 and 20 years of experience, who were blinded to all technical informations regarding magnetic fields strength and contrast injection rates.

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For the evaluation of image quality (degree of artifacts - GIBBS phenomenon) in early arterial and parenchymal arterial phases, we used a 4-point rating scale (1-4), similarly to the scale previously reported [17].

The quality was assigned as excellent (4) if no artifacts were observed; good (3) when mild artifacts were shown, but it did not interfere with image interpretation; poor (2) when moderate artifacts were observed and they did interfere with the

interpretation; and non diagnostic (1), when severe artifacts were observed impairing the assessment (Image 4).

Statistical analysis

Data were analyzed descriptively using mean, standard deviation, minimum and maximum values for continuous variables, and absolute and relative frequencies for categorical variables. The analysis of variance was used to test the effect of type of magnetic field, contrast agent injection rate and their interaction. If the interaction term did not reach statistical significance, the single effect were tested.

The effect of the same variables on artifacts was analyzed with a Chi-square test. A value of p<0.05 was considered as statistically significant. No adjustment was introduced to make allowance for multiple tests.

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RESULTS

Out of 435 submitted to MR studies, 249 patients satisfied eligibility criteria.

Patients were divided into four groups, on the basis of the type of magnetic field they were submitted to and on the basis of rate injection of contrast agent, as follow:

a) Group I – 1.5T and 1.5ml/s (77 patients; mean age: 59.9±11.4ys; range, 40-81 ys) b) Group II – 1.5T and 3mL/s (89 patients; mean age: 60.1±11.4ys; range, 35-86 ys) c) Group III - 3.0T and 1.5mL/s (34 patients; mean age: 65.6±9.6ys; range, 52-82 ys) d) Group IV - 3.0T and 3mL/s (49 patients; mean age: 61±10.4ys; range, 41-79 ys). There were no significant differences in the mean age nor in clinical data of the

patients among the four groups (Table 2).

Dynamic MRI study was performed in 166 patients using a superconducting magnet operating at 1.5T (Signa Twin; GE Healthcare, Milwaukee, Wis), with a 40 mT/m gradient strength (maximum slew rate, 120 mT/m/s) and 12-element surface phased-array coil.

In 83 patients, dynamic MRI was performed using a superconducting magnet

operating at 3.0T (DISCOVERY MR750; GE Healthcare), with a 50 mT/m gradient strength (maximum slew rate, 200 T/m/s) and 8-element surface phased-array coil. Mean duration of both arterial phases was 14 sec (±3sec).

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Quantitative analysis-Enhancement Ratios

ERs of target structures of four groups are reported on Table 3.

Contrast injection flow rates resulted not to influence ERs of liver parenchymas on early arterial nor on parenchymal arterial phases, independently from magnetic field strenght (Table 4), nor other target structures ERs on dedicated phases (Table 5). Magnetic field strenght instead, resulted to significantly influence (p <0.0001) ERs of liver on parenchymal arterial and portal venous phase (3T better than 1.5T MRI). Quantitative analysis-Signal to Noise Ratios

SNR of liver parenchymas on both arterial phases resulted not to be influenced by contrast agent injection rate (p values 0.4455 - early arterial; 0.1938 - parenchymal arterial phases), independently from magnetic field strength (Table 6).

SNR resulted instead strictly dependent from magnetic field strenght, also on baseline acquisition (1.5T greater than 3T MRI: p <0.0001).

Qualitative analysis

Distribution of artifacts on the basis of contrast injection rates and magnetic field strength are reported on Table 7.

Image quality resulted not to be dependent from contrast agent injection rate (p: 0.7710).

The percentage of good quality MR examinations (artifacts degrees 3 or 4) was not dependent by the two different injection flow rates in the two subsequent arterial phases (respectively: 1.5ml/sec: 70,27% and 81,08%; 3ml/sec 74.63% and 84.05%).

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Of notice, MR studies acquired at 1.5T resulted to have better image quality in parenchymal arterial phase than studies acquired at 3T MRI (p 0.0355); no magnetic field effect on image quality was appreciable on early arterial phase.

DISCUSSION

Gd-EOB-DTPA is a paramagnetic, hepatobiliary contrast agent, characterized by a high relaxivity in human plasma (6.9L mmol−1 s−1 at 1.5T MRI) [4]; because of this peculiarity, even a small amount of contrast determines a strong shorten of tissues’ relaxation T1 times [18].

That peculiarity reflects in the possible break of the k-space filling and homogeneity, especially in cases in which an adequate MR protocol study is not performed.

Many variables can affect MR imaging quality and detection of target structures enhancements during dynamic studies, such as adopted sequence parameters (for example, fat saturation technique, matrix, phase FOV), contrast injection flow rate and optimization of acquisition times.

As reported, the abrupt flow of a strong paramagnetic molecule, such as gadolinium, might lead to the inhomogeneity of the magnetic field and then to the presence of artifacts during the acquisition of arterial phase, that consisting in a poor image quality [19].

Despite in clinical use since some years, no definite consensus about Gd-EOB-DTPA administration flow rate nor a standardized protocol for the acquisition of arterial phase for the study of the liver have been settled yet.

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Several recent studies have been conducted in order to determine which is the best tecnical approach to administer Gd-EOB-DTPA as, for example, by means of contrast diluition method or slow injection rate [10-11].

Some authors report that diluition method can avoid the presence of ringing artifacts during the acquisition of arterial phase, because of the reduction of the magnetic effect of the agent, due to the quite complete filling of the central k space at the time of contrast arrival; on the contrary, the conventional injection method (pure contrast agent, followed by saline chaser flush) is considered at high risk of artifacts, because of the strong inhomogenity of the B0 field due to contrast arrival [11].

To avoid such collateral effects, the majority of authors suggest to proceed to the intravenous administration of Gd-EOB-DTPA by means of a slow injection rate (0.7-1ml/sec) [20-21].

Moreover, a number of studies have been conducted in order to assess which is the best acquisition protocol for the arterial phase; particularly, aside the frequently used fixed scan delay method, consisting in the acquisition of a single parenchymal arterial phase at a time variable between 30 up to 40 sec after contrast agent injection, the bolus triggering technique had been proposed in order to avoid arterial phase missing due to wrong sincronization to the cardiac output of patients [10-11].

Anyway, some authors have reported another technical approach to compensate for temporal mismatch of the acquisition of the arterial phase, consisting in the

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This method has been proved to furnish a reliable arterial vascular study, by providing arterial data set suitable for lesion characterization in the majority of studies (about 95%) [1].

Our study has been conducted on a population of 249 patients, in whom Gd-EOB-DTPA had been administered at two different flow injection rates (1.5mL/sec: 111 patients and 3ml/sec: 138 patients), by means of automatic injection of a precise dose, on the basis of the real patient body weight (0.025mmol/Kg).

All dynamic studies had been conducted by means of a “modified fixed time delay protocol”, consisting into two subsequent arterial phases (early arterial and

parenchymal arterial), in order to compare the effects of different injection flows on the parenchymal enhancements.

On the basis of our results, different flow injection rates resulted not to influence liver parenchymas ERs on both arterial phases (respectively: p 0.9573 and p 0.0308) or portal venous phase (p 0.0281), nor other target structures ERs (aortic lumens on both arterial phases, nor portal vein lumen and spleen parenchyma on portal venous

phase).

Moreover, velocity of contrast agent injection did not result to alter the incidence of artifacts on both arterial phases, especially regarding the presence of grade 1 and 2.

One possible explanation for the low incidence of artifacts in our studies,

independently from contrast flow rate injection, can be the adoption of dedicated, optimized sequences, that reduce the time of acquisitions, as well as the application of pre saturation pulses, in order to reduce flow artifacts from vessels. Moreover, in

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our studies, we did increase the number of phase-encoding steps (256 or greater), in order to reduce the prominence of truncation artifacts [1].

The adoption of ZIP (ZIP 2 and ZIP512x512) allows the possibility to increase the number of phase-encoding steps of the 3D acquisition sequence (LAVA), so reducing the time of imaging acquisition for each phase, that leading to the reduction of

artifacts.

The performance of a “modified fixed scan delay protocol”, consisting into two subsequent arterial phases, allows to reduce the possibility of the mismatch between contrast injection and the acquisition of the proper arterial phase, since with this method, it is possible to cover a large amount of time (from 15 up to 45 seconds) after contrast agent administration, so to have two different sets of arterial phases, and then reducing the possibility to miss the right arterial acquisition.

By applying high flow injection rates (3ml/sec), as in our series, even a full dose (10 mL of Gd-EOB-DTPA) is injected within 3 seconds and all the injected dose

(contrast and saline chaser-20ml at the same flow rate), is administered within 10 seconds, that represents the time by which the bolus stretch through the central veins, cardiopulmonary system, and thoracic aorta [22].

This time might be considered substantially shorter than the data acquisition time (usually 12-16 seconds); anyway, by the time of starting the acquisition of the early arterial phase with “modified fixed scan delay protocol”, at 15sec after injection, contrast injection had been finished since at least 12 seconds, during which it has

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distributed to target structures and the maximum peak of aortic enhancement has passed.

Moreover, by acquiring two arterial, subsequent phases, the necessity to obtain the filling of the centre of the k-space coinciding with the arrival of the bolus in the main portal vein to achieve a late arterial phase should be considered as a less critical factor in order to avoid artifacts.

In our experience, the availability of more than one arterial phase data set allows a more precise assessment of the arterial enhancement pattern of focal liver lesions, leading to improved characterization and diagnostic confidence.

Of notice, in our population, differencies of ERs was instead observed on the basis of the magnetic field applied (3 T vs 1.5T MRI). In fact, we did observe a significantly better ER of livers on parenchymal arterial and portal venous phase, that might be explained because of the well know increase of the better CNR in post-contrast images obtained at a 3T scan, attributable to behavior and effectiveness of contrast agents at 3T versus 1.5T, on the basis of the relaxivity of the paramagnetic ion complex and tissue relaxation times, both of which vary with field strength.

Because T1 times at 1.5T are shorter than at 3T, an equivalent dose of contrast at 3T appears to cause more of a contrast difference. A possible explanation for the lack of this effect on the early arterial phase can be due to the fact that during this early acquisition, the alteration of tissue T1 relaxation times are less influenced since the contrast do distribute mainly into arterial vessels and hyperenhancing lesions. Moreover, in our study, despite applying in both machines LAVA sequences, it

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should be noticed that at 3T MRI we did use a LAVA Flex sequence, characterized by a different fat suppression method (DIXON algorithm), that leads to a better enhancement ratio of analyzed structures.

In our study, we moreover find out that SNR of liver parenchymas on both arterial phases was not influenced from injection flow rates. Instead, also in this case, the magnetic field strength (1.5T more than 3T) did result to affect the image signal. Despite it is well know that structures’ signal increases when they are introducted in higer magnetic field strenght, the application of large matrix, even if it’s responsible for a better image quality in terms of spatial resolution, and limitation of artifacts, might determine the increase of the noise.

CONCLUSION

On the basis of obtained data, we can assess that the velocity of flow injection rate of contrast agent do not affect the ERs nor the SNR of analyzed structures and particularly of the liver parenchymas.

An optimized acquisition protocol allows a low incidence of high grade artifacts (grade 1 and 2), independently from flow injection rate.

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TABLES

Table 1: 1.5T and 3T LAVA sequence parameters

1.5T (Lava XV) 3T (Lava FleX)

TR-Repetition Time 3.5 3.0

TE-Echo Time 1.7 1.5

NEX 0.50-1 0.50-1

Flip Angle 12 12

Matrix 258x144* 352x168*

Slice thickness 5.2mm (ZIP2; ZIP512x512: 2.6mm)

4.2mm (ZIP2: 2.1mm)

Phase FOV (%) 70-90 70-90

Range of acquisition From the thoraco-abdominal

passage to the carrefour From the thoraco-abdominal passage to the carrefour

Encoding Phase A-P A-P

* Matrix related to phase FOV, but always greater than 256

Table 2: Patients data

1.5T-1.5ml/s N=77 1.5T-3ml/s N=89 3T-1.5ml/s N=34 3T-3ml/s N=49 Age (yrs) 59.9±11.4 (40-81) 60.1±11.4 (35-86) 65.6±9.6 (52-82) 61±10.4 (41-79) Sex Female Male 21 56 24 65 9 25 12 37 Child-Pugh A B 58 (75.3%) 19 (24.7%) 54 (60.7%) 35 (39.3%) 5 (14.7%) 29 (85.3%) 25 (51%) 24 (49%) Serum creatinine (mg/dL) 0.85 0.83 0.80 0.79 Serum Albumine (g/dL) 3.8±0.4 3.5±0.5 3.0±0.4 2.9±0.6 Serum Bilirubine tot (mg/dL) 1.1±0.8 1.3±0.5 1.7±0.4 1.5±0.5

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Table 3: Target structures Enhancement Ratios.

Structure Phase 1.5T-1.5ml/sec (77) 1.5T-3ml/sec (89) 3T-1.5ml/sec (34) 3T-3ml/sec (49)

Liver Early arterial 0.080±0.132 0.076±0.135 0.108±0.153 0.119±0.174 Parenchymal arterial 0.524±0.168 0.490±0.188 0.670±0.223 0.579±0.194 Portal venous 0.625±0.171 0.585±0.171 0.778±0.329 0.686±0.186 Portal vein lumen Portal venous 2.455±0.617 2.405±0.507 2.393±1.064 2.046±0.723 Spleen Portal venous 1.086±0.330 1.110±0.345 0.901±0.527 0.986±0.344 Aorta (thoraco-abdominal passage) Early arterial 3.990±1.785 4.024±2.525 4.098±2.062 3.673±2.215 Parenchymal arterial 2.258±0.827 2.6±4.054 2.858±1.315 2.661±1.617 Aorta (coeliak trunk) Early arterial 5.059±2.006 5.075±2.402 4.308±2.050 3.864±2.517 Parenchymal arterial 2.878±0.837 3.322±4.206 2.342±1.299 2.023±1.236 Aorta (renal

arteries) Early arterial 4.507±2.116 4.435±2.294 3.832±2.086 3.496±2.517 Parenchymal

arterial

2.638±1.005 3.056±4.204 2.166±1.344 1.837±1.270

Table 4: Liver enhancements by contrast agent injection rate (1.5ml/sec vs 3ml/sec) and by magnetic field strength (1.5T vs 3T MR).

Liver Injection

rate Strength Field

1.5ml/sec (111) 3ml/sec (138) P value 1.5T (166) 3T (83) P value Early arterial 0.089±0.139 0.091±0.151 0.9573 0.078±0.133 0.115±0.164 0.0584 Parenchymal arterial 0.569±0.198 0.522±0.194 0.0308 0.506±0.180 0.616±0.210 <.0001

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Table 5: target structures ERs by contrast agent injection rate (1.5ml/sec vs 3ml/sec) and by magnetic field strength (1.5T vs 3T MR).

Structure Phase Injection rate Field strength 1.5ml/sec (111) 3ml/sec (138) P value 1.5T (166) 3T (83) P value

Liver Portal venous 0.672 ± 0.240 0.621±0.182 0.0281 0.603±0.172 0.724± 0.256 <0.0001

Portal vein lumen

Portal venous 2.436 ± 0.777 2.278±0.615 0.0945 2.428±0.559 2.188 ±0.890 0.0124 Spleen Portal venous 1.029 ± 0.407 1.066±0.348 0.3563 1.099±0.337 0.951±0.428 0.0030

Aorta (thoraco-abdomin al passage) Early arterial 4.023±1.865 3.899±2.417 0.6773 4.008±2.206 3.847± 2.151 0.6011 Parenchymal arterial 2.442±1.034 2.621±3.387 0.6213 2.441±3.018 2.742± 1.495 0.4084 Aorta (coeliak trunk) Early arterial 4.829±2.040 4.645±2.503 0.6416 5.068±2.221 4.046±2.334 0.0010 Parenchymal arterial 2.714±1.026 2.861±3.505 0.5688 3.116±3.132 2.154±1.264 0.0072 Aorta (renal arteries) Early arterial 4.300±2.121 4.102±2.409 0.5835 4.468±2.207 3.634±2.342 0.0070 Parenchymal arterial 2.493±1.134 2.623±3.502 0.6142 2.862±3.152 1.971 ±1.303 0.0135

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Table 6: Signal to Noise Ratios of Liver Parenchymas by contrast agent injection rate (1.5ml/sec vs 3ml/sec) and by magnetic field strenght (1.5T vs 3T MR).

Liver Injection

rate

Field

Strength 1.5ml/sec

(111) 3ml/sec (138) P value (166) 1.5T (83) 3T P value

Baseline - - - 10.084(± 3.164) 19.309 (± 10.334) <0.0001 Early arterial 22.725 (±11.483) 21.059 (± 11.742)) 0.4455 26.720 (± 10.999) 12.032 (± 4.515) <0.0001 Parenchymal arterial 32.698 (±16.704) 29.397 (±16.479) 0.1938 37.611(± 16.003) 17.482 (± 6.909) <0.0001

Table 7: Distribution of imaging artifacts by contrast agent injection rate (1.5ml/sec vs 3ml/sec) and by magnetic field strength (1.5T vs 3T MR).

Liver- phase Degree of artifact Injection rate Field strength Early arterial 1.5ml/sec (111) 3ml/sec (138) 1.5T (166) 3T (83) 1 9 (8.11%) 4 (2.90%) 9 (5.42%) 4 (4.82%) 2 24 (21.62%) 31 (22.46%) 36 (21.69%) 19 (22.89%) 3 60 (54.05%) 83 (60.14%) 88 (53.01%) 55 (66.27%) 4 18 (16.22%) (14.49%) 20 (19.88%) 33 (6.02%) 5 Parenchymal arterial 1 (1.80%) 2 (0.72%) 1 (1.20%) 2 (1.20%) 1 2 19 (17.12%) 21 (15.22%) 23 (13.86%) 17 (20.48%) 3 75 (67.57%) 100 (72.46%) 115 (69.28%) 60 (72.29%) 4 15 (13.51%) 16 (11.59%) 26 (15.66%) 5 (6.02%)

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IMAGES

b

a

c

d

Image 1: Circular standard Regions of Interest (ROIs) were drawn in order to measure the Signal Intensities (SI) of liver parenchyma on unenhanced (a), early arterial (b), parenchymal arterial (c) and portal venous phase (d).

ROIs positioned in the liver parenchyma had a predefinite area of 150mm2 and were drawn in predefinite locations (periphery of the VII, VIII, IV and III segment), at the level of the bifurcation of the portal vein.

In order to perform a correct and reproducible measurement for each case, an automatic positioning of the ROIs in the selected areas simultaneously in the four different phases of acquisition (unenhanced, early arterial, parenchymal arterial, venous phase) was performed.

When the ROI was set, great care was taken to exclude the large vessels, to minimize any errors in SI measurements from macroscopic flow. The average values of SI of liver parenchyma were then calculated for each acquisition phase, to be used for data analysis.

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a

b c d

e f g

Image 2.1: Circular, standard Regions of Interest (ROIs) of a predefinite area of 150mm2 in order to measure the Signal Intensities (SI) were drawn on abdominal aortic lumen at the level of the thoraco-abdominal passage, of the emergency of the coeliak trunk and at the emergency of renal arteries on unenhanced (a, at thoraco-abdominal passage), early arterial (b, c, d) and on parenchymal arterial phase (e, f, g). In order to perform a correct and reproducible measurement for each case, we did apply an automatic positioning of the ROIs simultaneously in the different phases of acquisition (unenhanced, early arterial, parenchymal arterial).

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a b

c d

Image 2.2: Standard Regions of Interest (ROIs) in order to mesure the Signal Intensities (SI) were drawn on the portal vein lumen at the level of its extraepatic tract on the unenhanced (a) and portal venous phase (c) and also on the splenic parenchyma on unenhanced (b) and on the portal venous phase (d).

ROIs’ areas in the portal vein were as large as possible, on the basis of vessel caliber.

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a b

Image 3: Image noise was measured as SD of a ROI outside the body volume along the phase-encoding direction on baseline acquisition (a): particularly, in order to avoid in all cases the aorta artifact (b), ROI were positioned at a distance of 1.5cm, on the right side of the image.

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a

b

c

d

Image 4: For the evaluation of image quality (degree of artifacts-GIBBS

phenomenon) in early arterial and parenchymal arterial phases, we used a 4-point rating scale (1-4).

The quality was assigned as excellent (4) if no artifacts were observed (a); good (3) when mild artifacts were shown, but it did not interfere with image interpretation (b); poor (2) when moderate artifacts were observed and they did interfere with the

interpretation (c); and non diagnostic (1), when severe artifacts were observed impairing the assessment (d).

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REFERENCES

1. Ringe KI, Husarik DB, Sirlin CB et al. Gadoxetate disodium-enhanced MRI of the liver: part 1, protocol optimization and lesion appearance in the

noncirrhotic liver. AJR Am J Roentgenol 2010 Jul; 195(1): 13-28.

2. Cruite I, Schroeder M, Merkle EM et al. Gadoxetate disodium-enhanced MRI

of the liver: part 2, protocol optimization and lesion appearance in the cirrhotic liver. AJR Am J Roentgenol 2010 Jul; 195(1): 29-41.

3. Tamada T, Ito K, Higaki A, Yoshida K et al. Gd-EOB-DTPA-enhanced MR imaging: evaluation of hepatic enhancement effects in normal and cirrhotic livers. Eur J Radiol 2011 Dec; 80(3): 311-6.

4. Verloh N, Haimerl M, Zeman F et al. Assessing liver function by liver

enhancement during the hepatobiliary phase with Gd-EOB-DTPA-enhanced MRI at 3 Tesla. Eur Radiol 2014 May; 24(5): 1013-9.

5. Ringe KI, Boll DT, Husarik DB et al. Lesion detection and assessment of

extrahepatic findings in abdominal MRI using hepatocyte specific contrast agents-comparison of Gd-EOB-DTPA and Gd-BOPTA. BMC Med Imaging 2013 Mar 18; 13: 10.

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6. Kim MJ, Kim SH, Kim HJ et al. Enhancement of liver and pancreas on late hepatic arterial phase imaging: quantitative comparison among multiple gadolinium-based contrast agents at 1.5 Tesla MRI. J Magn Reson Imaging 2013 Jul; 38(1): 102-8.

7. Frydrychowicz A, Lubner MG, Brown JJ et al. Hepatobiliary MR imaging with gadolinium-based contrast agents.

J Magn Reson Imaging 2012 Mar; 35(3): 492-511.

8. Haradome H, Grazioli L, Tsunoo M et al. Can MR fluoroscopic triggering technique and slow rate injection provide appropriate arterial phase images with reducing artifacts on gadoxetic acid-DTPA (Gd-EOB-DTPA)-enhanced hepatic MR imaging? J Magn Reson Imaging 2010 Aug; 32(2): 334-40.

9. Schmid-Tannwald C, Herrmann K, Oto A et al. Optimization of the dynamic, Gd-EOB-DTPA-enhanced MRI of the liver: the effect of the injection rate. Acta Radiol 2012 Nov 1; 53(9): 961-5.

10. Tamada T, Ito K, Yoshida K et al. Comparison of three different injection methods for arterial phase of Gd-EOB-DTPA enhanced MR imaging of the liver. Eur J Radiol 2011 Dec; 80(3): 284-8.

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11. Motosugi U, Ichikawa T, Sou H et al. Dilution method of gadolinium

ethoxybenzyl diethylenetriaminepentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI). J Magn Reson Imaging 2009 Oct; 30(4): 849-54.

12.  Nakamura S1, Nakaura T, Kidoh M et al. Timing of the hepatic arterial phase at Gd-EOB-DTPA-enhanced hepatic dynamic MRI: comparison of the test-injection and the fixed-time delay method. J Magn Reson Imaging 2013 Sep; 38(3): 548-54.

13. Pietryga JA, Burke LM, Marin D et al. Respiratory motion artifact affecting hepatic arterial phase imaging with gadoxetate disodium: examination recovery with a multiple arterial phase acquisition. Radiology 2014 May; 271(2) :426-34.

14. Talakic E, Steiner J, Kalmar P et al. Gd-EOB-DTPA enhanced MRI of the liver: correlation of relative hepatic enhancement, relative renal enhancement, and liver to kidneys enhancement ratio with serum hepatic enzyme levels and eGFR Eur J Radiol 2014 Apr; 83(4): 607-11.

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comparison of 3.0T and 1.5T MR imaging of the liver in patients with diffuse parenchymal liver disease. Eur J Radiol 2009 Nov; 72(2): 314-20.

16. Lee VS, Lavelle MT, Rofsky NM, et al. Hepatic MR imaging with a dynamic contrast-enhanced isotropic volumetric interpolated breath-hold examination: feasibility, reproducibility, and technical quality. Radiology 2000; 215: 365– 372.

17. Tanimoto A, Higuchi N, Ueno A. Reduction of ringing artifacts in the arterial phase of gadoxetic acid-enhanced dynamic MR imaging. Magn Reson Med Sci 2012; 11(2): 91-7.

18. Reimer P, Rummeny EJ, Shamsi K et al. Phase II clinical evaluation of Gd-EOB-DTPA: dose, safety aspects, and pulse sequence. Radiology 1996 Apr; 199(1): 177-83.

19. Elster AD, Burdette JH. Questions & Answers in Magnetic Resonance Imaging . Mosby 2001

20. Davenport MS, Viglianti BL, Al-Hawary MM et al. Comparison of acute transient dyspnea after intravenous administration of gadoxetate disodium and gadobenate dimeglumine: effect on arterial phase image quality. Radiology

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201(1):97-107.

22. Davenport MS, Caoili EM, Kaza RK et al. Matched within-Patient Cohort Study of Transient Arterial Phase Respiratory Motion-related Artifact in MR Imaging of the Liver: Gadoxetate Disodium versus Gadobenate Dimeglumine. Radiology 2014 Jul; 272(1): 123-31.

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