Signal Enhancement of Gadoquatrane for Standard Clinical Pulse Sequences

Abstract

Objectives:

The purpose of this phantom study in human plasma was to characterize the signal enhancement properties of gadoquatrane under clinically relevant, highly standardized conditions in comparison to gadobutrol. Gadoquatrane is a novel high-relaxivity, extracellular macrocyclic gadolinium-based contrast agent (GBCA) currently in clinical development at a dose of 0.01 mmol/kg body weight (corresponding to 0.04 mmol Gd/kg).

Materials and Methods:

Three GBCA-dilution series in human plasma were prepared: 2 series with equimolar Gd concentrations (0-10 mmol Gd/mL) for gadoquatrane (0.4 mol Gd/L) and gadobutrol (1.0 mol Gd/L), and 1 series with 60% lower Gd concentrations for gadoquatrane (12 samples/series). For each series, signal intensity versus Gd concentration profiles were obtained using standard T1-weighted MRI pulse sequences at 1.5 T. In addition, the impact of sequence parameters was investigated (repetition and echo time for spin-echo sequences; flip angle for gradient-echo sequences).

Results:

The signal enhancement achieved with the 2 GBCAs depended on the Gd concentration and the pulse sequence. For all sequences tested, almost superimposable signal intensity profiles were found for gadobutrol and gadoquatrane, with 60% lower Gd concentrations for gadoquatrane. Sequence parameter variations affected both GBCAs in the same way. The optimal flip angles were equal for gadobutrol and gadoquatrane (60% reduced).

Conclusions:

The signal intensity profiles obtained in human plasma using standard clinical pulse sequences were almost superimposable for gadobutrol and gadoquatrane at 60% lower Gd concentrations. For clinical use, this means that the same pulse sequence parameters can be used for both GBCAs and that, essentially, the same signal enhancement can be expected from gadoquatrane at a dose of 0.04 mmol Gd/kg body weight as from gadobutrol at a dose of 0.1 mmol Gd/kg.

Signal intensity (SI) and, consequently, image contrast are key parameters for the diagnostic performance in magnetic resonance imaging (MRI). They can be enhanced by the use of gadolinium-based contrast agents (GBCAs), which alter the magnetic properties of tissues and body fluids.^1,2 The magnitude of the achieved signal enhancement depends on (1) the Gd concentration in the target region or area of interest,^2,3 (2) the relaxivity of the GBCA,^2,4,5 and (3) MRI parameters such as pulse sequence.^6,7 The GBCA concentration in the target region or area of interest depends on the pharmacokinetic properties of the agent, individual patient parameters such as cardiovascular physiology,⁸ and contrast injection-related parameters such as dose^9–11 and injection rate.^12,13 The relaxivity (r1, r2) of a GBCA is a measure of its ability to shorten the intrinsic tissue relaxation time (T1, T2). The shortening generally leads to an increase in SI and contrast. For GBCAs, T1 shortening is the dominant effect. Contrast-enhanced MRI is usually performed with task- and body region-specific T1-weighted pulse sequences. To minimize the MRI-related Gd exposure as recommended by regulatory authorities¹⁴ and medical guidelines, 2 new, high-relaxivity macrocyclic GBCAs have been developed that can be used at lower Gd doses than established GBCAs such as gadobutrol: gadopiclenol, which already received marketing approval,¹⁵ and gadoquatrane, which is currently under regulatory assessment.

Gadoquatrane is a novel macrocyclic GBCA with high relaxivity and kinetic stability.^16,17 On the basis of its unique tetrameric structure, the r1-relaxivity is more than 2-fold higher than that of well-established macrocyclic GBCAs such as gadobutrol.¹⁷ Gadoquatrane to be used at a dose of 0.04 mmol Gd/kg body weight has recently been investigated in phase 3 studies and is currently under regulatory review by several health authorities. The pharmacokinetic properties of gadoquatrane, which determine its distribution and local concentration, are essentially the same as those of other macrocyclic GBCAs.^10,18–20 This means that GBCA relaxivity and MRI parameters become decisive factors for SI or contrast enhancement when patient- and injection-related factors are kept constant. Standardized investigations in phantoms offer the opportunity to evaluate the impact of these factors and exclude factors such as patient physiology or GBCA injection protocols.

The aim of this phantom study in human plasma was to characterize the signal enhancement properties of gadoquatrane under clinically relevant, highly standardized conditions in comparison to gadobutrol. For this purpose, SI versus Gd concentration profiles were obtained using standard T1-weighted clinical MRI pulse sequences. To ensure high clinical translatability, measurements were performed in human plasma at body temperature using a clinical scanner at 1.5 T. Before SI measurements, the r1 and r2 relaxivities of gadoquatrane were determined at 1.5 T as a supplement to previously reported relaxivity data.¹⁷

MATERIALS AND METHODS

Contrast Agents and Plasma Samples

Two GBCAs were investigated in this phantom study in human plasma: the investigational product gadoquatrane (Bayer AG) and gadobutrol as a reference. Gadoquatrane was used in the same formulation as in the pivotal phase 3 studies of gadoquatrane (QUANTI CNS, QUANTI OBR, QUANTI Pediatric; clinicaltrials.gov nos: NCT05915702, NCT05915728, NCT05915026). Gadobutrol was used in its commercial formulation (Gadovist; Bayer Vital GmbH). An overview of the key physicochemical properties of the 2 GBCAs is given in Table 1. In line with the higher relaxivity of gadoquatrane,¹⁷ the Gd concentration in the gadoquatrane formulation was 60% lower than in the gadobutrol formulation (0.4 vs. 1.0 mol Gd/L), so that the injection volume was the same for the gadoquatrane and gadobutrol doses investigated in the above-mentioned pivotal studies (0.1 mL/kg body weight, equivalent to 0.04 mmol Gd/kg body weight and 0.1 mmol Gd/kg, respectively).

TABLE 1.

Physiochemical Properties of the GBCAs

	Unit	Gadoquatrane	Gadobutrol
Gd concentration	mol Gd/L	0.4	1
r1 relaxivity	L/(mmol·s)	11.8* , †	5.2 ‡ , §
r2 relaxivity	L/(mmol·s)	14.7†	6.1‡ , §
Osmolality 37 °C	mOsm/kg H2O	320	1603
Viscosity 37 °C	mPas·s	1.54	4.96

^*Lohrke et al¹⁷

^†Determined at 1.41 T

^‡Rohrer et al²

^§Determined at 1.5 T

Human plasma for phantom MRI examinations was obtained from pooled heparinized blood from healthy volunteers (3 male/3 female). The plasma was stored frozen at −20 °C until shortly before the MRI examinations, when it was thawed, spiked with gadoquatrane or gadobutrol, and transferred into glass vials (4 mL).

For relaxation time measurements, plasma was spiked with gadoquatrane and gadobutrol, each at concentrations of 0, 0.125, 0.25, and 0.5 mmol Gd/L.

To evaluate the signal intensities, 3 different sample series were prepared (Fig. 1). Series 1 and 2 were used to compare gadoquatrane and gadobutrol at equimolar Gd concentrations ranging from 0 to 10 mmol Gd/L, while series 2 and 3 were used to compare the same GBCA-volume dilutions. Series 3 was prepared with gadoquatrane at 60% lower Gd concentrations than in series 1. The actual Gd concentrations of the individual samples were analyzed using inductively coupled optical emission spectrometry (ICP-OES, iCAP 7600; Thermo Fischer Scientific, Waltham, MA). The resulting concentration values were used for all analyses.

FIGURE 1.

Spin-echo images of the phantom setup for signal intensity profile measurements. Numbers indicate the nominal Gd concentration (mmol Gd/L). H₂O indicates blank water samples. Gadoquatrane was compared with gadobutrol at equimolar Gd concentrations and at equal volume dilutions, that is, at 40% of the Gd dose. GBCA indicates gadolinium-based contrast agent.

MRI

MRI was performed on a whole-body 1.5 T scanner (Avanto Fit; Siemens Healthineers, Forchheim, Germany) using a 20-channel head coil. The plasma samples were placed in a water-filled, tempered (37 °C) and thermally insulated phantom (Fig. 1).

Relaxation Time Measurements

Samples prepared for relaxation time measurements were imaged simultaneously. T1 relaxation times were measured using an inversion recovery turbo spin-echo pulse sequence with variable inversion times (TI) to determine longitudinal relaxation curves. In a second step, T2 relaxation times were measured using a multiecho spin-echo sequence to determine the transversal relaxation curves. For sequence parameters, see Table 2.

TABLE 2.

Relaxation Time Measurements: Sequence Parameters

	T1 relaxation time	T2 relaxation time
Sequence	Inversion recovery turbo spin echo	Multiecho spin echo
TR (ms)	5000+TI	3000
TE (ms)	7.7	8.5-272 32 echoes (8.5 ms spacing)
TI (s)	0.023, 0.05, 0.1, 0.15, 0.2, 0.3, 0.5, 0.7, 1.1, 1.6, 2.4, 4	—
Echo train length	9	—
Pixel spacing (mm2)	0.5×0.5	0.4×0.4
Slice thickness (mm)	10	8

TE indicates echo time; TI, inversion time; TR, repetition time.

Signal Intensity Measurements

Each of the sample series prepared to evaluate the SI versus concentration relationship was imaged separately. The following 4 routine clinical pulse sequences were applied at their standard settings: spin echo, turbo spin echo, fast low angle shot (FLASH), and volumetric interpolated breath-hold examination (VIBE). In a second step, parameters of spin-echo, FLASH, and VIBE sequences were varied to test the impact of the parameter settings on SI profiles. For details, see Table 3.

TABLE 3.

Signal Intensity Measurements: Sequence Parameters

	Spin echo	Turbo spin echo	FLASH	VIBE
TR (ms)/TE (ms)	500/8.7	550/6.8	10/4.8	5.8/2.8
FA (deg.)	90/180	90/150	20	10
Pixel spacing (mm²)	0.5×0.5	0.5×0.5	0.5×0.5	0.5×0.5
Slice thickness (mm)	5	5	2	2.5
Parameter variation	TR (ms): 350-650 (50 ms steps)		FA (deg.): 10-30 (2-degree steps)	FA (deg.): 2-30 (2-degree steps)
	TE (ms): 8.7, 10-20 (2 ms steps)

FA indicates flip angle; FLASH, fast low angle shot; TE, echo time; TI, inversion time; TR, repetition time; VIBE, volumetric interpolated breath-hold examination.

Image Evaluation and Postprocessing

All images were evaluated quantitatively on an external workstation (syngo.via; Siemens Healthineers). A 1-cm² region of interest was placed in the central slice of each sample for SI measurements.

Relaxation Time and Relaxivity

For each sample, T1 and T2 relaxation times were calculated by fitting the experimental SI to the absolute values given by the signal equations for inversion recovery spin-echo and multiecho spin-echo sequences, as described by Rohrer et al.² The GBCA concentration-dependent longitudinal relaxation times T1 were determined by:

$$\mathit{SI}\left(\mathit{TI}\right)={\mathit{SI}}_{\inf }·\left|1-2e^{-\frac{\mathit{\text{T}}\text{I}}{T1}}\right|,$$ (1)

where SI(TI) is the measured SI at the respective TI. SI _inf , SI at full relaxation, and T1 were allowed to vary during the fitting procedure. The transverse relaxation times T2 were determined by fitting the measured SI at the respective echo time (TE) to (SI(TE)) to:

$$\mathit{SI}\left(\mathit{TE}\right)={\mathit{SI}}_0·e^{-\frac{\mathit{TE}}{T2}}+{\mathit{SI}}_{\mathit{noise}},$$ (2)

where SI ₀ corresponds to the steady-state SI and SI _noise to the baseline noise level.

The r1 and r2 relaxivities, defined as the slopes of the linear regression between the GBCA concentration-dependent relaxation rate (1/T1, 1/T2) and the Gd concentration, were calculated with 95% CIs. All calculations, data fittings, and graphical analyses were performed using Microsoft Excel and Prism 10.0 (GraphPad Software Inc., La Jolla, CA).

Signal Intensity and Signal Enhancement

SI profiles for the above-specified 4 standard clinical pulse sequences were evaluated for gadoquatrane at reduced Gd concentrations (60% lower than the concentrations in the corresponding gadobutrol samples, ie, at equal GBCA-volume dilutions) and at the same molar Gd concentrations as gadobutrol. The relative peak signal enhancement (%) was calculated by normalizing the peak SI to that of the blank plasma sample.

In the second step, the impact of the sequence parameters TE, repetition time (TR), and flip angle (FA) (Table 3) on SI profiles was evaluated. In addition, the optimal FA (Ernst angle α _E)²¹ for the VIBE and FLASH sequences was determined graphically²² for clinically relevant GBCA concentrations.

RESULTS

Relaxivity

The measured SI for different TI and TE are in good agreement with the fitted relaxation curves (Figs. 2A, C). The linear regression of the relaxation rates in dependence of the Gd concentration showed high coefficients of determination (R ² >0.998), indicating a high goodness of the linear fits (Figs. 2B, D). The resulting r1-relaxivity was 11.7 L/(mmol·s) [95% CI: 10.7-12.7 L/(mmol·s)] for gadoquatrane and 5.2 L/(mmol·s) [95% CI: 4.8-5.7 L/(mmol·s)] for gadobutrol. The r2-relaxivity was 14.8 L/(mmol·s) [95% CI: 13.4-16.1 L/(mmol·s)] for gadoquatrane and 6.3 L/(mmol·s) [95% CI: 5.5-7.2 L/(mmol·s)] for gadobutrol.

FIGURE 2.

T1 and T2 relaxation curves and rates for different concentrations of gadoquatrane: (A) Measured signal intensities (symbols) for different inversion times and fitted T1 relaxation curves (lines). (B) Gd concentration-dependent slope of R1 relaxation rate (r1 relaxivity). (C) Measured signal intensities (symbols) for different echo times and fitted T2 relaxation curves (lines). (D) Gd concentration-dependent slope of R2 relaxation rate (r2 relaxivity). Dotted lines represent the 95% CI of linear regression. a.u. indicates arbitrary unit

Signal Intensity and Signal Enhancement

The SI versus Gd concentration curves (SI profiles) for both gadoquatrane and gadobutrol showed a nonlinear characteristic with an increase in SI until the peak value was reached, followed by a plateau phase and, finally, a decline in SI at higher Gd concentrations. Figures 3 and 4 illustrate that the shape of the SI profiles and the degree of signal enhancement depended on the combination of GBCA, Gd concentration, and pulse sequence applied.

FIGURE 3.

Signal intensity profiles acquired with different pulse sequences (A, spin echo; B, turbo spin echo; C, FLASH; D, VIBE) for gadoquatrane and gadobutrol at equimolar Gd concentrations. Error bars represent SDs. a.u. indicates arbitrary unit; FLASH, fast low angle shot; VIBE, volumetric interpolated breath-hold examination.

FIGURE 4.

Signal intensity profiles acquired with different pulse sequences (A, spin echo; B, turbo spin echo; C, FLASH; D, VIBE) for gadoquatrane and gadobutrol at equal GBCA-volume dilutions. The Gd concentrations are given in blue (gadoquatrane) and red (gadobutrol). Error bars represent SDs. a.u. indicates arbitrary unit; FLASH, fast low angle shot; VIBE, volumetric interpolated breath-hold examination.

The relative peak signal enhancement for spin-echo sequences (turbo spin-echo sequences) amounted to 443% (374%) for gadoquatrane and 436% (379%) for gadobutrol. These peak SIs were determined in the 0.5 mmol Gd/L sample for gadoquatrane and the 1.5 mmol Gd/L sample for gadobutrol. For gradient echo-based sequences, peak enhancement was found at higher concentrations, that is, in the 2 mmol Gd/L sample for gadoquatrane and the 4 mmol Gd/L sample for gadobutrol. The final SI decline was more pronounced for spin echo-based than for gradient echo-based sequences. The peak enhancement for FLASH (VIBE) sequences was 1043% (358%) for gadoquatrane and 1082% (375%) for gadobutrol.

The comparison of gadoquatrane and gadobutrol with equal GBCA-volume dilutions, that is, with 60% lower Gd concentrations for gadoquatrane, yielded almost superimposable SI profiles for both GBCAs and for all pulse sequences (Fig. 4). Peak enhancement was seen for both agents in the 1.5 mL/L sample for the spin-echo sequences, that is, at a concentration of 0.6 mmol Gd/L for gadoquatrane and 1.5 mmol Gd/L for gadobutrol, and in the 4 mL/L sample for the gradient echo-based sequences, that is, at 1.6 and 4 mmol Gd/L, respectively.

Variations of the spin-echo sequence parameters TR and TE affected the peak enhancement and the shape of the SI profiles of both GBCAs. Reducing TR or increasing TE resulted in reduced peak enhancement and shifted the peak to higher Gd concentrations. The effect of changes in TR was most prominent for lower concentrations (<0.8 mmol Gd/L for gadoquatrane and <2 mmol Gd/L for gadobutrol) (Fig. 5A). Changes of TE, in contrast, impacted SI only at higher dilutions (>0.2 mmol Gd/L for gadoquatrane and >0.5 mmol Gd/L for gadobutrol; Fig. 5B). For the gradient echo-based sequences, an increase in FA at given TR and TE values increased the peak enhancement. This effect was equally observed for gadobutrol and gadoquatrane, and the SI profiles were almost identical when equal GBCA-volume dilutions were used. For FLASH and VIBE sequences, the impact of the FA increased with the GBCA concentration and was pronounced for gadoquatrane concentrations >0.4 and >0.2 mmol Gd/L, respectively, and gadobutrol concentrations >1 and >0.5 mmol Gd/L, respectively (Figs. 5C, D). For gradient-echo sequences, the highest SI can be obtained at an FA equal to the Ernst angle. At equimolar sample concentrations (Fig. 6), it was higher for gadoquatrane than for gadobutrol, while it was identical for equal GBCA-volume dilutions. The Ernst angle determined for dilutions of 0.5 mL/L (corresponding to a Gd concentration of 0.5 mmol/L for gadobutrol and 0.2 mmol/L for gadoquatrane) was 14 degrees for FLASH as well as for VIBE image acquisitions.

FIGURE 5.

Impact of variations in pulse sequence parameters on signal intensity profiles for gadoquatrane and gadobutrol. The shaded areas represent the signal intensity ranges for (A) different repetition times, (B) different echo times, and (C, D) different flip angles. The Gd concentrations are given in blue (gadoquatrane) and red (gadobutrol). a.u. indicates arbitrary unit; FA, flip angle; FLASH, fast low angle shot; TE, echo time; TR, repetition time; VIBE, volumetric interpolated breath-hold examination.

FIGURE 6.

Impact of the parameter flip angle for (A) FLASH and (B) VIBE sequences on signal intensity for gadoquatrane and gadobutrol. Red lines and symbols indicate SI values determined for gadobutrol at a concentration of 0.5 mmol Gd/L; blue dotted lines and triangles indicate SI values determined for gadoquatrane at the same concentration. Blue solid lines and circles indicate SI values determined for gadoquatrane at a 60% lower Gd concentration (ie, at an equal GBCA-volume dilution as for gadobutrol). Error bars represent SDs. a.u. indicates arbitrary unit; FLASH, fast low angle shot; SI, signal intensity; TE, echo time; TR, repetition time; VIBE, volumetric interpolated breath-hold examination.

DISCUSSION

In this phantom study, we evaluated the signal enhancement properties of gadoquatrane, a novel high-relaxivity MRI contrast agent, under clinically relevant, highly standardized laboratory conditions. For all pulse sequences investigated, the peak signal enhancement was similar for both GBCAs at equimolar concentrations but shifted toward lower Gd concentrations for gadoquatrane in line with its higher relaxivity. At 60%-reduced Gd concentrations for gadoquatrane compared with gadobutrol (equal GBCA-volume dilutions), in contrast, almost identical SI profiles were observed. Variations of sequence parameters affected these dilution-dependent SI profiles equally for both GBCAs.

Gadobutrol served as a reference in our study, representing the group of clinically well-established macrocyclic GBCAs gadobutrol, gadoterate meglumine, and gadoteridol. As gadobutrol possesses the highest r1 relaxivity among the 3,⁴ it can be assumed that the signal enhancement achieved with gadoterate meglumine and gadoteridol does not exceed the enhancement achieved with gadobutrol (for concentrations <10 mmol/L). Gadobutrol at the standard dose of 0.1 mmol Gd/kg (as well as the other 2 GBCAs) was also used as a comparator in the above-mentioned QUANTI CNS and QUANTI OBR studies, where gadoquatrane was effectively used at a 60% lower dose (0.04 mmol Gd/kg).

The concept of Gd dose reduction using high-relaxivity agents has recently been confirmed in a phantom study of gadopiclenol,⁷ a newly approved high-relaxivity GBCA [r1/r2 relaxivity: 12.8/15.1 L/(mmol·s)].²³ In this study, the signal enhancement properties were investigated for several clinical pulse sequences, and the peak SI was found at about 50% lower Gd concentrations compared with other GBCAs such as gadobutrol. However, in contrast to our study, the quantitative results of this study comparing gadopiclenol to other GBCAs are not representative of the clinical situation, as they were obtained under nonphysiological conditions. GBCA dilutions were done with water instead of human plasma, and MRI was performed at room temperature and not at body temperature. Both diluent and temperature are known to strongly impact relaxivity and, in turn, the resulting signal enhancement in a GBCA-specific manner.^2,24

The context of our phantom study was used to evaluate the relaxivity of gadoquatrane at 1.5 T. The relaxivities determined were very similar to those obtained previously at 1.41 T,¹⁷ confirming that 60 MHz spectrometer-based relaxivity values are representative for the MRI-derived relaxivities at 1.5 T. Compared with gadobutrol, a 2.3-fold higher relaxivity for both r1 and r2 was found. The resulting similar r1/r2 ratios for gadoquatrane and gadobutrol explain the above-described similarity of the SI profiles, as signal enhancement depends on both r1 and r2 relaxivity.^2,25 The impact of r2 is known to increase with concentration, leading to a nonlinear relation between SI and Gd concentration.^6,7

In our study, we evaluated SIs at Gd concentrations that are to be expected following GBCA injection of 0.1 mmol Gd/kg (concentrations <2 mmol Gd/L for steady-state MRI^6,8,26 and <10 mmol Gd/L for MRA^3,27). In this range, a nonlinear relationship between SI and Gd concentration was seen. Only in a small concentration range below the peak enhancement, the SI-concentration graphs showed a linear relationship. Over the whole concentration range, distinct differences between the investigated pulse sequences existed. For the spin-echo sequences, for example, a much steeper increase in SI at low Gd concentrations was observed than for gradient echo-based sequences. In contrast, at higher concentrations above the peak enhancement, the SI immediately reversed instead of reaching a longer plateau phase as observed for the 2 gradient-echo sequences.

For our study, we used routine pulse sequences at the vendor-provided standard contrast-parameter settings (ie, TR, TE, and FA). However, in practice, these settings are modified depending on the clinical task,^28,29 the GBCA used,²⁵ the scanner configuration,³⁰ and site-specific preferences. To evaluate the impact of contrast-determining sequence parameters, variations of TR and TE (spin echo) and FA (FLASH, VIBE) were investigated. All alterations impacted the SI profiles of gadoquatrane and gadobutrol in the same manner and can be explained by the similar T1 and T2 shortenings for both GBCAs in combination with the sequence parameters. For spin echo-based sequences, TR and TE determine the T1 and T2 contrast, respectively. At Gd concentrations below the peak enhancement, shortening of TR results in an SI reduction as T1 is too long for full relaxation within the TR interval. The effect disappears with increasing concentration and, hence, stronger T1 shortening, and the SI becomes independent of TR. In contrast, with increasing TE, the T2 shortening at higher Gd concentrations is more pronounced and results in an SI reduction in the used T1-weighted spin-echo sequence. For gradient echo-based sequences, the FA at a given TR is most important. The SI at low Gd concentrations (<1 and <0.4 mmol Gd/L, respectively) is almost independent of the FA, while with increasing concentrations, a higher FA led to a higher SI. The optimal FA providing the highest SI for a given tissue T1 and TR is described by the Ernst angle.²² The T1 of the tissue depends on the native value and the GBCA-induced T1 shortening, which is determined by relaxivity and tissue Gd concentration. The latter, in turn, depends on the pharmacokinetics of the GBCA. Preclinical and clinical investigations demonstrated very similar pharmacokinetic profiles for gadoquatrane and gadobutrol.^10,17,19 To assess the optimal FA for the VIBE and FLASH sequences, we focused on clinically relevant Gd concentrations (0.5 and 0.2 mmol Gd/L for gadobutrol and gadoquatrane, respectively). This considers the different dosing in view of identical pharmacokinetics. The relationship between SI and FA was very similar for the 2 GBCAs, and the respective Ernst angles were identical. This demonstrates again that gadoquatrane at 60% lower Gd concentrations has very similar signal enhancement properties to gadobutrol. Overall, it can be assumed that the same pulse sequence parameters can be used for gadoquatrane as for gadobutrol.

That no adaptation of sequence parameters such as the FA is necessary cannot be taken for granted. For gadobutrol, for example, different Ernst angles are recommended than for Gd-DTPA or gadoterate meglumine.^25,31 Recently, a new GBCA-specific concept to optimize the acquisition parameters TR and FA for fast spoiled gradient-echo images was suggested.²⁵ It maximizes the image contrast between healthy and diseased tissue rather than optimizing the SI of the enhancing tissue only. On the basis of the above-described findings, we assume that the application of this strategy will also lead to identical acquisition parameters for gadobutrol and gadoquatrane at a 60%-reduced dose.

A limitation of our study is that we investigated the signal enhancement properties of gadoquatrane only at 1.5 T, the field strength of most clinical MRI units. This data should be complemented by systematic studies at other field strengths. Also, a wider range of specific pulse sequences, such as magnetization-prepared acquisitions, should be included in further studies.

CONCLUSIONS

The signal intensity profiles obtained in human plasma using standard clinical pulse sequences were almost superimposable for gadobutrol and gadoquatrane at 60% lower Gd concentrations. For clinical use, this means that the same pulse sequence parameters can be used for both GBCAs and that essentially the same signal enhancement can be expected from gadoquatrane at a dose of 0.04 mmol Gd/kg body weight as from gadobutrol at a dose of 0.1 mmol Gd/kg.