Gadopiclenol Versus Gadoterate Meglumine for Pediatric Brain MRI: An Intraindividual Comparison of Contrast Enhancement

Abstract

Background:

The macrocyclic agent gadopiclenol, FDA-approved in 2022, has relatively high T1 relaxivity, allowing substantial dose reductions.

Objective:

To perform an intraindividual quantitative and qualitative comparison of contrast enhancement between brain MRI examinations in children performed using gadopiclenol (0.05 mmol/kg) and gadoterate meglumine (0.1 mmol/kg).

Methods:

This retrospective study included 38 pediatric patients (mean age: 11.1 years; 25 male, 13 female) who underwent gadopiclenol-enhanced brain MRI (0.05 mmol/kg) from December 1, 2024 to March 31, 2025 and gadoterate meglumine-enhanced MRI (0.1 mmol/kg) within the prior 6 months using the same field strength and protocol. Data were separately analyzed for 3D T1-weighted fast-spin echo (FSE), 3D T1W gradient-recalled echo (GRE), and 2D FLAIR postcontrast sequences (27, 11, and 22 patients, respectively). Contrast ratio (CR) and CNR were measured in physiologic enhancing structures (choroid plexus, pituitary, dural venous sinuses, turbinate mucosa). Two neuroradiologists identified preferred sequence for characterizing enhancement of physiologic enhancing structures (choroid plexus, pituitary, dural venous sinuses, turbinate mucosa, dura mater) in side-by-side blinded comparisons using a Likert scale (−2 to 2).

Results:

CR was higher for gadopiclenol than for gadoterate for choroid plexus on 3D T1W FSE (71.0±17.8 vs 63.5±37.2, p=.04) and turbinate on 3D T1W GRE (81.7±21.8 vs 58.1±25.1, p=.01). Remaining comparisons of CR between the two agents were not significant (p>.05). CNR was not significantly different between the two agents for any combination of structure and sequence (P>.05). Both readers preferred gadopiclenol on 3D T1W FSE for choroid plexus (R1: −0.4±0.6, p=.005; R2: −0.5±0.8, p=.02) and pituitary (R1: −0.5±0.7, p<.001; R2: −0.5±0.9, p=.009). Reader 1 also preferred gadopiclenol on 3D T1W FSE for turbinate (−0.7±0.7, p<.001). Both readers preferred gadoterate meglumine on FLAIR for turbinate (R1: 0.3±0.5, p=.01; R2: 0.5±0.8, p=.02). Reader 2 also preferred gadoterate meglumine on FLAIR for choroid plexus (0.5±0.8, p=.01). Neither reader had a significant preference for either agent for remaining combinations of structure and sequence (p>.05).

Conclusion:

The findings support use of gadopiclenol at half the standard gadolinium dose for pediatric brain MRI examinations.

Clinical Impact:

Use of gadopiclenol could facilitate reductions in cumulative gadolinium exposure in children requiring serial MRI examinations.

Introduction

Pediatric brain MRI examinations commonly use gadolinium-based contrast agents (GBCAs) to evaluate vascular structures as well as to detect and characterize a spectrum of pathologic conditions that disrupt the blood-brain barrier [1,2]. However, safety concerns have emerged regarding deposition throughout the body of dechelated or transchelated gadolinium ions after GBCA exposure [3–5]. Although such deposition occurs primarily after administration of linear GBCAs, it also has been reported after the use of macrocyclic agents despite such agents’ greater chemical stability [3,6–8]. Data suggest that gadolinium deposits in the brain and cortical bone lack significant clinical consequences [4]. Nonetheless, special caution remains warranted regarding the use of GBCAs in children [4,5,9], who have a longer remaining life expectancy than adults and may therefore be subject to unrecognized adverse effects associated with long latency periods [9].

Gadopiclenol, marketed as Vueway by Bracco Diagnostics and Elucirem by Guerbet, is a macrocyclic GBCA that received FDA approval in 2022. In comparison with prior macrocyclic agents, gadopiclenol has relatively greater chemical stability, theoretically improving its safety profile [10–14]. Specifically, the agent’s prolonged dissociation half-life, reportedly up to 20 days, facilitates its excretion before non-chelated gadolinium ions can deposit in organs[15]. In addition, gadopiclenol has greater T1 relaxivity than other macrocyclic agents, allowing a potential substantial reduction in administered gadolinium doses without a loss in tissue enhancement [10,15–17]. Two prospective industry-sponsored multicenter, randomized, double-blind, controlled, crossover phase 3 trials in adults (PROMISE [15] and PICTURE [18]) reported that gadopiclenol administered at a half gadolinium dose (0.05 mmol/kg) was clinically equivalent to the macrocyclic agent gadobutrol administered at a standard gadolinium dose (0.1 mmol/kg) for postcontrast T1-weighted (T1W) sequences in the brain and body [15,18].

Given the substantial differences in pathology and physiology between children and adults, as well unique aspects of the MRI protocols commonly used in pediatric brain imaging, dedicated studies are needed to support clinical adoption of gadopiclenol for brain MRI examinations in children. The two principal MRI sequences routinely used in pediatric neuroimaging to assess blood-brain barrier integrity and pathology are postcontrast T1W imaging and postcontrast FLAIR. For these sequences, gadopiclenol administered at a half gadolinium dose (0.05 mmol/kg) could potentially provide enhancement that is qualitatively and quantitatively comparable to that obtained from the macrocyclic agent gadoterate meglumine (marketed as Dotarem and Clariscan by Guerbet and GE Healthcare, respectively) administered at a standard gadolinium dose (0.1 mmol/kg), both in normal anatomic structures and in pathologic lesions.

The aim of this study was to perform an intraindividual quantitative and qualitative comparison of contrast enhancement between brain MRI examinations in children performed using gadopiclenol (0.05 mmol/kg) and gadoterate meglumine (0.1 mmol/kg).

Methods

This retrospective HIPAA-compliant study was conducted at Massachusetts General Hospital, a tertiary pediatric academic medical center. The institutional review board approved the study and granted a waiver of the requirement for written informed consent. All MRI examinations evaluated in the study had been performed solely for standard-of-care purposes. In December 2024, the study institution switched its GBCA for routine clinical MRI examinations in patients 2 years old and older from gadoterate meglumine to gadopiclenol.

The institutional PACS was searched for patients 2–18 years old who underwent a contrast-enhanced brain MRI examination using gadopiclenol between December 1, 2024, and March 31, 2025, yielding 102 patients. The search results were reviewed to identify those patients who also underwent a contrast-enhanced brain MRI examination using gadoterate meglumine within the 6 months before the gadopiclenol-enhanced examination, performed at the same field strength using the same protocol. This step identified 38 patients. Patients were then reviewed for potential exclusion based on the following criteria with respect to either of the two MRI examinations: incomplete examination; significant motion artifacts or other major technical limitation impairing diagnostic image quality; interval therapy that could alter lesion enhancement (e.g., tumor resection, chemotherapy initiation); evidence of interval disease progression. However, no patient was excluded based on any of these criteria. Thus, the final study sample included 38 pediatric patients who underwent both a gadoterate meglumine-enhanced brain MRI examination and a gadopiclenol-enhanced brain MRI examination. Figure 1 shows the flow of patient selection. Information recorded for all patients in the final study sample included age, sex, clinical induction for undergoing brain MRI, and interval between the two MRI examinations.

Fig. 1-.

Patient selection flowchart. T1W = T1-weighted, FSE = fast spin echo; GRE = gradient-recalled echo

MRI Examinations

MRI examinations were performed using a 1.5-T scanner (SIGNA Artist, General Electric Healthcare, USA) with a 20-channel head coil or a 3-T scanner (MAGNETOM Prisma Fit, Siemens Healthineers, Erlangen, Germany) with a 32-channel head coil. All examinations were performed in accordance with standard institutional pediatric brain MRI protocols. Depending on the selected protocol, the two examinations may have included an axial 2D postcontrast fast spin echo (FSE) FLAIR sequence. All examinations also included a postcontrast 3D T1W sequence. Based on the selected protocol, the 3D T1W sequence for the two examinations was a 3D T1W FSE sequence (SPACE [Siemens] or CUBE [GE HealthCare]) or a 3D T1W gradient-recalled echo (GRE) sequence (MRPAGE). The examinations included additional sequences that were not evaluated as part of the present examination. Gadopiclenol and gadoterate meglumine were each administered at their respective clinically approved doses (0.05 and 0.1 mmol/kg, respectively). For all examinations, the GBCA injection was followed, in order, by an axial FSE T2W sequence (not evaluated in the present investigation), FLAIR sequence, and 3D T1W FSE or 3D T1W GRE sequence.

Quantitative Assessment

A pediatric neuroradiologist (C.J, 8 years of posttraining experience) and a research fellow (M.C) used a joint process to place ROIs on the MRI examinations to perform a quantitative assessment, blinded to the contrast agent used for each examination. The neuroradiologist first identified the slices on which ROIs would be placed, selecting one slice or two contiguous slices for each evaluated structure (as described later in this section). As part of this slice selection process, the neuroradiologist assessed the examinations for the presence of a focal enhancing lesion. The research fellow, who had undergone an initial training session from the neuroradiologist, then placed the ROIs, which were stored on the images. Finally, the pediatric neuroradiologist reviewed the stored ROIs and optionally adjusted their positioning. The frequency with which the neuroradiologist adjusted ROI positioning was not recorded. Figure S1 shows examples of ROI placement.

Using this process, for each examination, a single ROI was placed within the choroid plexus, pituitary, dural venous sinuses, and mucosa of the turbinates (hereafter, turbinate) [19] representing structures showing physiologic enhancement. Single ROIs were also placed within normal-appearing white matter (WM), extracranial image background, and any focal enhancing lesion detected during the neuroradiologist’s review. For the dural venous sinuses, ROIs were placed only on the 3D T1W GRE sequence because this structure show enhancements only on this sequence; the structure was not evaluated in patients who underwent MRI using a 3D T1W FSE sequence. For the other structures, ROIs were placed separately on the 3D T1W sequence (FSE or GRE) and the FLAIR sequence (if performed). The two examinations were reviewed concurrently for a given patient, and efforts were made to place matching ROIs on the two examinations for each evaluated combination of structure and sequence.

The mean signal intensity was recorded for each ROI, aside from the ROI of extracranial image background; for the latter ROI, SD was recorded as a measure of image noise. For each evaluated structure for each examination (aside from WM and extracranial image background), the contrast ratio was calculated for applicable sequences using the formula: $\text{CR}=\left(100\times \left({\text{WM}}_{\text{mean}}-{\text{Structure}}_{\text{mean}}\right)\right)/\left(0.5\times \left({\text{WM}}_{\text{mean}}-{\text{Structure}}_{\text{mean}}\right)\right)$ [20]. Additionally, for each evaluated structure for each examination (aside from WM and extracranial image background), CNR was calculated for applicable sequences using the formula: $\text{CNR}=\left({\text{Structure}}_{\text{mean}}-{\text{WM}}_{\text{mean}}\right)/{\text{Background}}_{\text{SD}}$ [21]. The cross-sectional area of each ROI was also recorded.

Qualitative Assessment

Two board-certified pediatric neuroradiologists (C.J [R1], the previously noted investigator; S.F [R2], with 2 years of posttraining experience) independently reviewed the MRI examinations to perform a qualitative assessment. The readers were presented with pairs of sequences displayed on a double-screen diagnostic monitor, corresponding with matching sequences from the patient’s two examinations (gadopiclenol and gadoterate meglumine). Specifically, for each patient, the radiologists were presented with a pair representing the 3D T1W sequences (FSE or GRE) from the two examinations or a pair representing the FLAIR sequences (if performed) from the two examinations. The selection of which sequence was placed on the left versus on the right monitor was determined randomly for each presented pair. The radiologists were permitted to freely scroll through the displayed sequences in each pair. The radiologists were blinded to which examination (i.e., which GBCA) corresponded with the sequence on each monitor.

For each displayed sequence pair, the readers assigned a single score on a 5-point Likert scale from −2 to 2 to characterize enhancement of the choroid plexus, enhancement of the pituitary, enhancement of the dural venous sinuses, enhancement of the turbinate, and enhancement of the dura mater. The dural venous sinuses were assessed only on 3D T1W GRE sequences because, as previously noted, the structure shows enhancement only on this sequence. The readers were also informed if the sequence pair were from a patient with a focal enhancing lesion; in such instances, the readers also assigned scores using the same 5-point Likert scale to characterize the lesion’s border delineation, contrast enhancement, and internal morphology, as described by Loevner et al. [18]. For all of these assessments, a score of 0 indicated no preference between the two sequences, +1 indicated a slight preference for the image on the right monitor, and +2 indicated a strong preference for the image on the right monitor; negative numbers indicated corresponding preferences for the images on the left monitor.

After the readers had completed their assessments, the previously noted research fellow decoded the scores to assign the readers’ preferences to the corresponding agent. For purposes of subsequent data analysis and presentation, negative scores were uniformly used to indicate a preference for gadopiclenol, and positive scores were uniformly used to indicate a preference for gadoterate meglumine.

Statistical Analysis

Data were summarized using descriptive statistics including counts and frequencies, as well as means and SDs. CR and CNR were summarized for each combination of agent, structure, and sequence (FLAIR, 3D T1W FSE, 3D T1W GRE). The Shapiro-Wilk test was used to determine the normality of the distributions of CR and CNR. These metrics were compared were between the two agents using paired t tests or Wilcoxon signed-rank tests for normal and nonnormal distributions, respectively. The readers’ Likert scores were summarized for each combination of structure and sequence (FLAIR, 3D T1W FSE, 3D T1W GRE). Wilcoxon signed-rank tests were used to assess if readers’ scores showed significant differences from a score of zero. Statistical significance testing was not performed for results regarding focal enhancing lesions a given very small sample size for such assessments. ROI cross-sectional areas were also compared between the two agents using a paired t test or Wilcoxon signed-rank test. A p value less than .05 was considered statistically significant. Statistical analyses were conducted using SPSS software (version 24), and graphical representations were created in RStudio (version 4.4.1).

Results

Patients and Examinations

Table 1 summarizes characteristics of the study sample of 38 patients. A total of 25 (66%) patients were male, and 13 (34%) were female. The patients’ mean age was 11.1 ± 4.9 years (range, 3–18 years). The most common indication was postsurgical follow-up (12 [31.6%] patients). Both examinations were performed at 1.5 T in 15 (40%) patients, and both at 3 T in 23 (60%) patients. The mean interval between the two examinations was 32.3 ± 26.9 days (range, 1.6–70.9 days). Both the gadopiclenol-enhanced examination the gadoterate meglumine-enhanced examinations included a 3D T1W FSE sequence in 27 patients, both included a 3D T1W GRE sequence in 11 patients, and both included a FLAIR sequence in 22 patients.

Table 1:

Study sample characteristics in 38 patients.

Variable	Value
Age (y), mean ± SD	11.1 ± 4.9
Sex
Male	25 (66)
Female	13 (34)
Clinical indication for MRI
Postsurgical follow-up	12 (31.6)
Brain tumor	9 (23.7)
Epilepsy or seizure	6 (15.8)
Neurocutaneous syndrome	5 (13.2)
Multiple sclerosis	2 (5.3)
Leukodystrophy	1 (2.6)
Lymphangiomatosis	1 (2.6)
Vasculopathy	1 (2.6)
Sinusitis	1 (2.6)
MRI field strength
1.5 T	15 (40)
3 T	23 (60)
Interval between MRI examinations (d), mean ± SD	32.3 ± 26.9
Availability of sequences on both examinations
3D T1W FSE	27 (71.1)
3D T1W GRE	11 (28.9)
FLAIR	22 (57.9)
Presence of focal enhancing lesion	4 (10.5)

Unless otherwise indicated, data expressed as count with percentage in parentheses.

T1W = T1-weighted; FSE = fast spin echo; GRE = gradient-recalled echo

Based on the review by the pediatric neuroradiologist, the MRI examinations showed a single focal enhancing lesion in four patients. For these four patients, both examinations included a 3D T1W FSE sequence and a FLAIR sequence. No examination showed multiple enhancing lesions.

Quantitative Analysis

Table S1 summarizes the volumes of the ROIs placed for the quantitative analysis. For both 3D T1W sequences (pooling FSE and GRE acquisitions) and FLAIR sequences, the ROI cross-sectional areas were not significantly different between the two examinations for any structure (all p>.05).

Table 2 summarizes the comparison of CR and CNR between the gadopiclenol-enhanced and gadoterate meglumine-enhanced examinations. CR was significantly higher for gadopiclenol-enhanced examinations than for gadoterate meglumine-enhanced examinations for the choroid plexus on 3D T1W FSE images (71.0 ± 17.8 vs 63.5 ± 37.2, p = .04) and the turbinate on 3D T1W GRE images (81.7 ± 21.8 vs 58.1± 25.1, p = .01). CR was higher for gadopiclenol-enhanced than for gadoterate meglumine-enhanced examinations on 3D T1W GRE images, but this difference was not statistically significant (66.0 ± 37.7 vs 46.9 ± 20.8, p = .06). Remaining comparisons between the two agents on 3D T1W FSE and 3D T1W GRE images were not statistically significant (all p>.05). CR was not significantly different between the two examinations for any structure on FLAIR images (all p >.05). Additionally, CNR was not significantly different between the two agents for any combination of structure and sequence (all P > .05). Table S2 summarizes these results stratified by field strength.

Table 2:

Comparison of contrast ratio (CR) and CNR between gadoterate meglumine-enhanced and gadopiclenol-enhanced examinations

Structure, Sequence, Agent	n	CR, Mean ± SD		p	CNR, Mean ± SD		p
Choroid plexus
T1W 3D FSE	27			.04			.40
Gadoterate meglumine		63.4 ± 37.2			171.7 ± 231.8
Gadopiclenol		71.0 ± 17.8			131.0 ± 122.0
T1W 3D GRE	11			.13			.59
Gadoterate meglumine		62.4 ± 18.8			135.3 ± 77.3
Gadopiclenol		87.7 ± 16.3			404.7 ± 645.7
FLAIR	22			.43			.70
Gadoterate meglumine		44.9 ± 55.9			63.9 ± 60.0
Gadopiclenol		51.1 ± 26.3			57.6 ± 39.2
Pituitary
T1W 3D FSE	27			.07			.19
Gadoterate meglumine		45.13 ± 31.3			85.4 ± 83.1
Gadopiclenol		58.7 ± 14.4			105.5 ± 88.7
T1W 3D GRE	11			.06			.48
Gadoterate meglumine		46.9 ± 20.8			101.8 ± 81.4
Gadopiclenol		66.0 ± 37.7			265.1 ± 517.6
FLAIR	22			.80			.37
Gadoterate meglumine		15.8 ± 24.2			21.2 ± 25.7
Gadopiclenol		19.1 ± 21.3			17.6 ± 19.3
Dural venous sinuses
T1W 3D GRE	11			.14			.77
Gadoterate meglumine		72.7 ± 23.8			176.0 ± 115.5
Gadopiclenol		97.5 ± 13.3			395.5 ± 479.5
Turbinate
T1W 3D FSE	27			.16			.34
Gadoterate meglumine		56.7 ± 35.6			118.1 ± 108.7
Gadopiclenol		72.4 ± 18.2			144.3 ± 126.9
T1W 3D GRE	11			.01			.15
Gadoterate meglumine		58.1 ± 25.2			124.1 ± 80.2
Gadopiclenol		81.7 ± 21.8			305.7 ± 424.4
FLAIR	22			.08			.05
Gadoterate meglumine		69.4 ± 26.4			97.2 ± 71.5
Gadopiclenol		52.8 ± 34.8			63.1 ± 47.0
Lesion
T1W 3D FSE	4			-			-
Gadoterate meglumine		50.2 ± 18.8			77.1 ± 97.9
Gadopiclenol		87.9 ± 31.5			206.3 ± 117.1
FLAIR	4			-			-
Gadoterate meglumine		69.4 ± 35.2			67.4 ± 42.9
Gadopiclenol		76.6 ± 44.5			94.7 ± 75.4

P values represent comparisons between agents using paired t test for normally distributed data and Wilcoxon signed-rank test for nonnormally distributed data.

T1W = T1-weighted; FSE = fast spin echo; GRE = gradient-recalled echo

For the four lesions, CR on T1W 3D FSE images was 87.9±31.5 for gadopiclenol-enhanced examinations versus 50.2±18.8 for gadoterate meglumine-enhanced examinations; and on FLAIR images was 76.6±44.5 for gadopiclenol-enhanced examinations versus 69.4±35.2 for gadoterate meglumine-enhanced examinations. For the four lesions, CNR on T1W 3D FSE was was 206.3±77.1 for gadopiclenol-enhanced examinations versus 117.1±97.9 for gadoterate meglumine-enhanced examinations; and on FLAIR images was 94.7±75.4 for gadopiclenol-enhanced examinations versus 67.4±42.9 for gadoterate meglumine-enhanced examinations.

Figures S2 and S3 graphically summarize the CR and CNR results, respectively.

Qualitative Analysis

Table 3 summarizes results of the qualitative analyses. Both readers had a significant preference for gadopiclenol to characterize enhancement of the choroid plexus (R1: −0.4 ± 0.6, p=.005; R2: −0.5 ± 0.8, p=.02) and pituitary (R1: −0.5 ± 0.7, p<.001; R2: −0.5 ± 0.9, p=.009) on 3D T1W FSE images. Reader 1 also had a significant preference for gadopiclenol to characterize enhancement of the turbinate on 3D T1W FSE images (−0.7 ± 0.7, p<.001). Both readers had a significant preference for gadoterate meglumine to characterize enhancement of the turbinate on FLAIR images (R1: 0.3 ± 0.5, p=.01; R2: 0.5 ± 0.8, p=.02). Reader 2 also had a significant preference for gadoterate meglumine to characterize enhancement of the choroid plexus on FLAIR images (0.5 ± 0.8, p=.01). Neither reader had a significant preference for either agent for remaining combinations of structure and sequence (all p<.05).

Table 3:

Comparison of readers’ subjective preferences, as assessed by Likert scores, between gadoterate meglumine-enhanced and gadopiclenol-enhanced examinations

Structure, Sequence	n	Reader 1		Reader 2
		Mean ± SD	p	Mean ± SD	p
Choroid plexus
T1W 3D FSE	27	−0.4 ± 0.5	.005	−0.5 ± 0.8	.02
T1w 3D GRE	11	−0.1 ± 0.6	> .99	−0.3 ± 0.7	.17
FLAIR	22	0.0 ± 0.6	.71	0.5 ± 0.8	.01
Pituitary
T1W 3D FSE	27	−0.5 ± 0.7	< .001	−0.5 ± 0.9	.009
T1W 3D GRE	11	0.0 ± 0.7	.60	−0.5 ± 0.9	.35
FLAIR	22	0.1 ± 0.4	.33	0.2 ± 0.5	.10
Dural venous sinuses
T1W 3D GRE	11	−1.0 ± 1.0	.23	−0.3 ± 1.2	.67
Turbinate
T1W 3D FSE	27	−0.3 ± 0.7	.06	−0.7 ± 0.7	< .001
T1W 3D GRE	11	−0.4 ± 0.5	.08	−0.4 ± 0.5	.08
FLAIR	22	0.3 ± 0.5	.01	0.5 ± 0.8	.02
Dura mater
T1W 3D FSE	27	−0.1 ± 0.5	.67	−0.3 ± 0.7	.05
T1W 3D GRE	11	−0.1 ± 0.4	.35	0.0 ± 0.5	> .99
FLAIR	22	−0.1 ± 0.2	.33	0.1 ± 0.5	.43
Border delineation
T1W 3D FSE	4	−1.0 ± 1.0	-	−1.0 ± 1.0	-
FLAIR	4	−0.5 ± 0.7	-	−0.5 ± 0.7	-
Contrast enhancement
T1W 3D FSE	4	−1.0 ± 1.7	-	−1.0 ± 1.0	-
FLAIR	4	−0.5 ± 0.7	-	0.0 ± 1.4	-
Internal morphology
T1W 3D FSE	4	−0.3 ± 0.6	-	−0.7 ± 1.2	-
FLAIR	4	0.0 ± 0.0	-	0.0 ± 1.4	-

P values represent comparisons of means with score of zero using Wilcoxon signed-rank test.

T1W = T1-weighted; FSE = fast spin echo; GRE = gradient-recalled echo

For the four focal enhancing lesions, both readers had a preference (not assessed for statistical significance) for gadopiclenol for border delineation on T1W 3D FSE images (R1: −1.0±1.0; R2: −1.0±1.0), border delineation on FLAIR images (R1: −0.5±0.7; R2: −0.5±0.7), contrast enhancement on T1W 3D FSE images (R1: −1.0±1.7; R2: −1.0±1.0), and internal morphology on T1W 3D FSE images (R1: −0.3±0.6; R2: −0.7, 1.2). Reader 1 also had a preference for contrast enhancement on FLAIR images (−0.5±0.7). Neither reader had a preference (i.e., mean score, 0) for either agent for remaining lesion-related assessments.

Figure 2 graphically summarizes the readers’ qualitative assessments. Figure 3 and Figure S4 show examples of readers’ scores for 3D T1W and FLAIR images for gadopiclenol-enhanced and gadoterate meglumine-enhanced examinations. Figure 4 shows an example of the appearance of a lesion on FLAIR and 3D T1W images for both GBCAs.

Fig. 2 –

Violin plots summarizing distributions of readers’ Likert scores, stratified by reader, sequence, and structure, for 3D T1W FSE (A), 3D T1W GRE (B), and FLAIR (C) images. Negative values indicate preference for gadopiclenol-enhanced examination, whereas positive values indicate preference for gadoterate meglumine-enhanced examination. T1W = T1-weighed; FSE = fast spin echo; GRE =gradient-recalled echo.

Fig. 3-.

10-year-old boy who underwent brain MRI examinations for clinical indication of sinusitis. (A-C) Axial postcontrast FLAIR images from examination performed using gadoterate meglumine shows choroid plexus (arrow, A; reader scores of 0 and 1), pituitary (arrow, B; reader scores of 0 and 1), and turbinate (arrow, C; reader scores of 0 and 0). (D-F) Axial postcontrast FLAIR images from examination performed using gadopiclenol shows choroid plexus (arrow, D; reader scores of 0 and 1), pituitary (arrow, E; reader scores of 0 and 1), and turbinate (arrow, F; reader scores of 0 and 0). Negative values indicate preference for gadopiclenol-enhanced examination, whereas positive values indicate preference for gadoterate meglumine-enhanced examination.

Fig. 4-.

10-year-old boy who underwent brain MRI examinations due to optic tract glioma. (A,B) Axial postcontrast 3D T1W FSE (A) and FLAIR (B) images from examination performed using gadoterate meglumine. (C,D) Axial postcontrast 3D T1W GRE (C) and FLAIR (D) images from examination performed using gadopiclenol. Images show expansile lesion centered in left optic tract, with punctate enhancement medially and posteriorly (arrow, A-D). Readers 1 and 2 assigned score for border delineation on 3D T1W FSE of −2 and −1; for border delineation on FLAIR of 0 and 0; for contrast enhancement on 3D T1W FSE of −2 and −2; for contrast enhancement on FLAIR of 0 and 1; for internal morphology on 3D T1W FSE of −1 and −2; and for internal morphology on FLAIR of 0 and 0. Negative values indicate preference for gadopiclenol-enhanced examination, whereas positive values indicate preference for gadoterate meglumine-enhanced examination. T1W = T1-weighted; FSE =fast spin echo; GRE = gradient-recalled echo.

Discussion

In this retrospective non-industry-sponsored study, we performed an intraindividual comparison in 38 pediatric patients who underwent brain MRI examinations using gadopiclenol at half the standard gadolinium dose (0.05 mmol/kg) and gadoterate meglumine at the standard gadolinium dose (0.1 mmol/kg) within a 6-month period. Gadopiclenol yielded significantly greater CR in a couple of anatomic structures, whereas gadoterate meglumine did not yield significantly greater CR in any assessed structure. CNR was not significantly different between the two agents for any structure. In two readers’ side-by-side assessments of image sets from the two examinations to identify a preferred agent for characterizing enhancement of anatomic structures, the majority of assessments did not yield a significant preference for either agent; nonetheless, each agent was preferred by one or both readers for a small number of structures. In four patients with enhancing lesions, greater CR, CNR, and reader preference was observed for gadopiclenol, although these comparisons were not assessed for statistical significance given the very small number of lesions. The findings overall support the use of gadopiclenol as an alternative to other macrocyclic agents for pediatric brain MRI examinations.

The chemical structure of gadopiclenol permits a higher number of bound water molecules per Gd³⁺ ion in comparison with other GBCAs, including macrocyclic GBCAs, resulting in greater T1 relaxivity. This higher relaxivity in turn allows the administration of a relatively lower weight-based dose of gadolinium when using gadopiclenol. The increase in relaxivity, even in the setting of a lower administered gadolinium dose, can account for the present study’s observation of a significantly greater CR for a couple of structures for gadopiclenol. For such structures, the greater CR for gadopiclenol was observed only for certain 3D T1W images (FSE or GRE, depending on the structure) but not for FLAIR images, consistent with sequences’ varying sensitivities to the T1 shortening effects of gadolinium [22,23]. These findings align with the analysis of readers’ subjective preferences, in which readers preferred gadopiclenol for several structures, but likewise only on certain 3D T1W images.

The present results complement findings from two industry-sponsored, prospective, randomized controlled trials in adults, PROMISE [15] and PICTURE [18]. In those trials, gadopiclenol and gadobutrol, at half and standard gadolinium doses, respectively, provided comparable enhancement metrics and clinical performance for brain and abdominal MRI examinations. In the present study, CNR was not significantly different between the two tested agents, an observation that could suggest minimal impact of the increased relaxivity of gadopiclenol when accounting for background noise. On the other hand, the PICTURE trial reported significantly greater CNR for gadopiclenol with respect to gadobutrol [18]. This discrepancy may relate to the PICTURE trial’s larger sample size and/or primary use of a lesion-based CNR analysis; that lesion-based approach may have been more sensitive than the present study’s focus on physiologic enhancement, as areas of pathologic blood brain disruption may enable accumulation of larger concentrations of GBCA.

Relative to prior studies comparing gadopiclenol with other GBCAs, the present study is novel in its evaluation of postcontrast FLAIR images. FLAIR is a widely used sequence in pediatric neuroradiology, endorsed by multiple consensus guidelines for treatment response assessment in pediatric neurooncology [24]. In the present study, CR and CNR were not significantly different between gadopiclenol-enhanced and gadoterate meglumine-enhanced examinations for any structure for FLAIR images. However, one or both readers had a significant preference for gadoterate meglumine for the choroid plexus and turbinate on FLAIR images. We hypothesize that these differences may relate to factors beyond T1 relaxivity, such as T2* effects. Specifically, the longer TE of FLAIR images, compared to conventional 3D T1W images, may lead to greater sensitivity to T2* effects. Furthermore, the highly vascularized nature of the choroid plexus and turbinate mucosa may accentuate these putative T2* effects due to higher concentrations of GBCA within image voxels.

Pediatric patients may require serial contrast-enhanced brain MRI examinations for the diagnosis, treatment planning, and follow-up of a variety of CNS conditions, including neoplasms, inflammatory disorders, and vascular abnormalities. However, serial GBCA administration has been associated with gadolinium deposition in the brain and other tissues, including in patients with normal renal function [7] and in patients exposed to macrocyclic agents [4,25]. Gadopiclenol has relatively higher chemical stability than other macrocyclic agents, representing an additional advantage beyond its greater relaxivity. Nonetheless, improvements in tissue retention and long-term safety as a result of this greater stability remain largely theoretic. Confounding such safety assessments is the variable deposition of GBCAs across organs. In a study using mass spectroscopy in rats, overall gadolinium exposure over the course of 5 months after administration was lower for gadopiclenol than for either gadobutrol or gadoterate meglumine. Yet, while gadopiclenol was associated with the lowest gadolinium exposure in bone marrow, it was associated with the highest exposure in mineralized bone [25]. Even if the impact of the greater chemical stability of gadopiclenol is uncertain, the ability to administer lower gadolinium doses because of the agent’s greater relaxivity will lead to lower cumulative gadolinium exposures in patients undergoing serial examinations.

This study had limitations. First, it was conducted retrospectively at a single institution, introducing selection bias with respect to the institution’s referral patterns for pediatric brain MRI. Second, the analysis entailed quantitative and qualitative assessments of the enhancement of various structures; diagnostic performance was not evaluated. Third, within the context of the study’s focus on enhancement, the analysis evaluated primarily physiologic enhancing structures, accompanied by an assessment of enhancing lesions in only four patients. Distinct enhancement patterns could be observed in the setting of specific diseases and pathologic entities, such as leptomeningeal disease, which were not systematically evaluated in the present study. Third, gadopiclenol was compared solely with gadoterate meglumine, reflecting the agents routinely used at the study institution before and after a switch in agents in December 2022, respectively. In contrast, the available literature has compared gadopiclenol primarily with gadobutrol, a macrocyclic agent with higher relaxivity than gadoterate meglumine [15,18]. Fourth, the interval between the gadoterate meglumine-enhanced and gadopiclenol-enhanced examinations varied across patients. Although this variability is unlikely to have affected enhancement of normal anatomic structures, it could have introduced differences in enhancement in the four lesions analyzed. Fifth, not all reader preferences corresponded with a significant difference in CR. Such findings may have reflected a subtle difference in the texture of enhancement that was appreciable upon readers’ review of the complete sequences but not captured by a focal ROI-based analysis. Sixth, the quantitative analysis was based on only a single set of ROI measurements, obtained from a joint process among two observers. Finally, in the United States, the per-vial cost of Elucirem is currently higher than that of Dotarem [26]. However, improvements in image quality resulting from the use of gadopiclenol could potentially lead to downstream savings to offset this greater per-vial cost. This issue could be further assessed by cost-effectiveness analyses, cost-savings evaluations, and ecologic studies.

Conclusion

In this study, we performed an intraindividaul comparison of gadopiclenol at a dose of 0.05 mmol/kg and gadoterate meglumine at a dose of 0.1 mmol/kg for pediatric brain MRI examinations. A small number of quantitative comparisons yielded favorable results for gadopiclenol (all on 3D T1W images), with the remaining quantitative comparisons yielding no significant difference between the two agents. Additionally, a small number of qualitative comparisons yielded favorable results for gadopiclenol (all on 3D T1W images) or for gadoderate meglumine (all on FLAIR images), with the remaining qualitative comparisons yielding no significant difference between the two agents. These findings support the use of gadopicenol for pediatric brain MRI examinations, aiding reductions in cumulative gadolinium exposure in children requiring serial MRI examinations.

Highlights.

Key Finding:

In an intraindividual comparison of pediatric brain MRI examinations performed using gadopiclenol at half gadolinium dose and gadoterate meglumine at standard gadolinium dose, many qualitative and quantitative comparisons of contrast enhancement were not significantly different between agents; each agent showed a significantly better result in a small number of assessments.

Importance:

The high-relaxivity agent gadopiclenol enables substantially reduced gadolinium dosing, thereby offering an alternative for pediatric patients requiring serial brain MRI examinations.