Investigative Radiology最新文献

{"title":"Deuterium Metabolic Imaging of the Human Abdomen at Clinical Field Strength.","authors":"Pascal Wodtke, Mary A McLean, Ines Horvat-Menih, Jonathan R Birchall, Maria J Zamora-Morales, Ashley Grimmer, Elizabeth Latimer, Marta Wylot, Rolf F Schulte, Ferdia A Gallagher","doi":"10.1097/RLI.0000000000001170","DOIUrl":"10.1097/RLI.0000000000001170","url":null,"abstract":"<p><strong>Objectives: </strong>The aim of the study was to translate abdominal deuterium metabolic imaging (DMI) to clinical field strength by optimizing the radiofrequency coil setup, the administered dose of deuterium ( 2 H)-labeled glucose, and the data processing pipeline for quantitative characterization of DMI signals over time. This was assessed in the kidney and liver to establish a basis for routine clinical studies in the future.</p><p><strong>Materials and methods: </strong>5 healthy volunteers were recruited and imaged on 2 or 3 separate occasions, with varying doses of 2 H-glucose: 0.75 g/kg (high dose), 0.50 g/kg (medium dose), and 0.25 g/kg (low dose), resulting in a total of 13 DMI scan sessions. DMI was performed at 3 T using a flexible 20 × 30 cm 2 2 H-tuned transmit-receive surface coil. For quantitative comparisons across scans, the 2 H-glucose signal was normalized against the sum of 2 H-glucose and 2 H-water (GGW ratio). To quantify the time course of GGW, 3 novel metrics of metabolism were defined and compared between doses and organs: the maximum value across the time course (GGW max ), the sum over the whole time course (GGW AUC ), and the average signal across a defined plateau (GGW mean plateau ). The 2 H-lipid signal overlaps with 2 H-lactate; hence, the 2 signals were measured as the combined 2 H-lipid+lactate signal.</p><p><strong>Results: </strong>The careful positioning of a dedicated surface coil minimized unwanted gastric signals while maintaining excellent hepatic and renal measurements. The time courses derived from the liver and kidney were reproducible and comparable across different doses, showing the potential for dose reduction. The signal from the liver plateaued at approximately 30 minutes, and that from the kidney at approximately 40 minutes. The liver exhibited higher quantitative values for 2 H-glucose uptake compared to the kidney, a trend consistent across all 3 quantitative metrics and doses, for example, for the highest dose: GGW AUC liver  = 31 ± 3; GGW AUC kidney  = 27 ± 3; P  = 0.05. A trend toward lower quantitative measurements with decreasing dose was observed: this was significant between the high and the low dose for all 3 parameters and between the medium and low dose for GGW mean plateau and GGW AUC , but was not significant between the high and the medium dose for any of the 3 parameters. The hepatic 2 H-lipid+lactate signal increased over 70-90 minutes in 12/13 cases (mean: 39 ± 24%), while the renal lipid+lactate signal increased in only 8/13 cases (mean: 5 ± 17%). The hepatic 2 H-water signal increased in all 13 cases (mean: 18 ± 10%), and the renal 2 H-water signal increased in only 10/13 cases (mean: 10 ± 13%).</p><p><strong>Conclusions: </strong>DMI of the human abdomen is feasible using a clinical magnetic resonance imaging system and the signal changes measured in the kidney and liver can serve as a reference for future clinical studies. The 2 H-glucose dose can be reduced from","PeriodicalId":14486,"journal":{"name":"Investigative Radiology","volume":" ","pages":"1-9"},"PeriodicalIF":7.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12662132/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143624808","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Balanced Steady-State Free Precession Enables High-Resolution Dynamic 3D Deuterium Metabolic Imaging of the Human Brain at 7T.","authors":"Sabina Frese, Bernhard Strasser, Lukas Hingerl, Elton Montrazi, Lucio Frydman, Stanislav Motyka, Viola Bader, Anna Duguid, Aaron Osburg, Martin Krssak, Rupert Lanzenberger, Thomas Scherer, Wolfgang Bogner, Fabian Niess","doi":"10.1097/RLI.0000000000001196","DOIUrl":"10.1097/RLI.0000000000001196","url":null,"abstract":"<p><strong>Objectives: </strong>Deuterium ( 2 H) metabolic imaging (DMI) is an emerging magnetic resonance technique to non-invasively map human brain glucose (Glc) uptake and downstream metabolism following oral or intravenous administration of 2 H-labeled Glc. The achievable spatial resolution is limited due to inherently low sensitivity of DMI. This hinders potential clinical translation. The purpose of this study was to improve the signal-to-noise ratio (SNR) of 3D DMI via a balanced steady-state free precession (bSSFP) acquisition scheme combined with fast non-Cartesian spatial-spectral sampling to enable high-resolution dynamic imaging of neural Glc uptake and glutamate+glutamine (Glx) synthesis of the human brain at 7T.</p><p><strong>Materials and methods: </strong>Six healthy volunteers (2 f/4 m) were scanned after oral administration of 0.8 g/kg [6,6']- 2 H-Glc using a novel density-weighted bSSFP acquisition scheme combined with fast 3D concentric ring trajectory (CRT) k-space sampling at 7T. Time-resolved whole brain DMI datasets were acquired for approximately 80 minutes (7 minutes per dataset) after oral 2 H-labeled Glc administration with 0.75 mL and 0.36 mL isotropic spatial resolution and results were compared to conventional spoiled Free Induction Decay (FID) 2 H-MRSI with CRT readout at matched nominal spatial resolution. Dynamic DMI measurements of the brain were accompanied by simultaneous systemic Glc measurements of the interstitial fluid using a continuous Glc monitoring (CGM) sensor (on the upper arm). The correlation between brain and interstitial Glc levels was analyzed using linear mixed models.</p><p><strong>Results: </strong>The bSSFP-CRT approach achieved SNRs that were up to 3-fold higher than conventional spoiled FID-CRT 2 H-MRSI. This enabled a 2-fold higher spatial resolution. Seventy minutes after oral tracer uptake comparable 2 H-Glc, 2 H-Glx, and 2 H-water concentrations were detected using both acquisition schemes at both, regular and high spatial resolutions (0.75 ml and 0.36 mL isotropic). The mean Areas Under the Curve (AUC) for interstitial fluid Glc measurements obtained using a CGM sensor was 509 ± 65 mM·min. This is 3.4 times higher than the mean AUC of brain Glc measurements of 149 ± 43 mM·min obtained via DMI. The linear mixed models fitted to assess the relationship between CGM measures and brain 2 H-Glc yielded statistically significant slope estimates in both GM (β 1  = 0.47, P  = 0.01) and WM (β 1  = 0.36, P  = 0.03).</p><p><strong>Conclusions: </strong>In this study we successfully implemented a balanced steady-state free precession (bSSFP) acquisition scheme for dynamic whole-brain human DMI at 7T. A 3-fold SNR increase compared to conventional spoiled acquisition allowed us to double the spatial resolution achieved using conventional FID-CRT DMI. Systemic continuous glucose measurements, combined with dynamic DMI, demonstrate significant potential for clinical applications. This could help imp","PeriodicalId":14486,"journal":{"name":"Investigative Radiology","volume":" ","pages":"49-58"},"PeriodicalIF":7.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12353933/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144010149","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Developing Magnetic Resonance Imaging Biomarkers of Neuroinflammation, Cognitive Impairment, and Survival Outcomes for Radiotherapy-Induced Brain Injury in a Preclinical Mouse Model.","authors":"Maya Teitz, Esteban Velarde, Xiaoju Yang, Shana Lee, Kristen Lecksell, Chantelle Terrillion, Adnan Bibic, Ethel J Ngen","doi":"10.1097/RLI.0000000000001173","DOIUrl":"10.1097/RLI.0000000000001173","url":null,"abstract":"<p><strong>Objective: </strong>Radiotherapy-induced brain injury (RIBI) is a chronic side effect that affects up to 90% of brain tumor survivors treated with radiotherapy. Here, we used multiparametric magnetic resonance imaging (MRI) to identify noninvasive and clinically translatable biomarkers of RIBI.</p><p><strong>Method: </strong>8-week-old female, immune competent BALB/c mice were stereotactically irradiated with a single dose of 80 Gy, at a dose rate of 1.7 Gy/minute. The irradiated mice were then monitored longitudinally with MRI, behavioral tests of learning and memory, and immunohistochemistry, in comparison to nonirradiated mice.</p><p><strong>Results: </strong>Three types of MRI biomarkers of RIBI were identified. A contrast-enhanced T 1 -weighted MRI biomarker was identified as being best suited to detect the onset of injury, by detecting changes in the blood-brain barrier (BBB) permeability. Maximum BBB permeability (18.95 ± 1.75) was detected with contrast-enhanced T 1 -weighted MRI at 1-month postirradiation in irradiated mice ( P  < 0.0001, n = 3). Interestingly, maximum neuroinflammation (24.14 ± 6.72) was also detected using IBA1 and CD68 immunohistochemistry at 1-month postirradiation in irradiated mice ( P  = 0.0041, n = 3). This simultaneous maximum BBB permeability and neuroinflammation detection also coincided with the detection of the onset of transient cognitive impairment, detected using the fear-conditioning behavioral test at 1-month postirradiation in irradiated mice compared to nonirradiated mice ( P  = 0.0017, n = 10). A T 2 -weighted MRI hyperintensity biomarker was also identified, and determined to be best suited to detect intermediate injury. Maximum T 2 -weighted MRI hyperintensity (3.97 ± 2.07) was detected at 2-month postirradiation in the irradiated mice compared to nonirradiated mice ( P  = 0.0368, n = 3). This T 2 -weighted MRI hyperintensity also correlated with maximum astrogliosis (9.92 ± 4.21), which was also detected at 2-month postirradiation using GFAP immunohistochemistry in the irradiated mice compared to nonirradiated mice ( P  = 0.0215, n = 3). Finally, T 2 -weighted and T 2 *-weighted MRI hypointensity biomarkers were identified as being best suited to detect late injury, from 4-month postirradiation. These biomarkers correlated with increased iron deposition from late vascular damage, which was validated with Perls' Prussian blue histology ( P  < 0.05, n = 3). These hypointense MRI biomarkers of late injury also preceded significant weight loss, severe cognitive impairment, and decreased survival in the irradiated mice compared to the nonirradiated mice.</p><p><strong>Conclusions: </strong>Here, we identified 3 types of translational MRI biomarkers of RIBI that could enable the noninvasive longitudinal evaluation of potential RIBI prophylactic and therapeutic agents. These translational MRI biomarkers could also play a pivotal role in the management of RIBI in brain tumor survivors.</p>","PeriodicalId":14486,"journal":{"name":"Investigative Radiology","volume":" ","pages":"10-25"},"PeriodicalIF":7.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12353168/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143648471","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ready for Routine: Homogeneous, High-Resolution, and Multicontrast Whole-Brain MRI at 7 Tesla in Short Scan Time With \"plug-and-Play\" pTx Sequences.","authors":"Jennifer Faber, Daniel Paech, Eberhard Pracht, Rüdiger Stirnberg, Philipp Ehses, Yannik Völzke, Daniel Löwen, Mónica Ferreira, Sascha Brunheim, Nicolas Boulant, Vincent Gras, Franck Mauconduit, Aurélien Massire, Pål Erik Goa, Laurent Lamalle, Theodor Rüber, Tobias Bauer, Gabor C Petzold, Julia Nordsiek, Matthias Schneider, Christina Schaub, Thomas Klockgether, Alexander Radbruch, Tony Stöcker","doi":"10.1097/RLI.0000000000001252","DOIUrl":"10.1097/RLI.0000000000001252","url":null,"abstract":"<p><strong>Background: </strong>7T MRI received FDA/CE clearance almost 7 years ago. However, until today, it has not yet been widely adopted in clinical routine. This is mainly due to field inhomogeneities that impede whole-brain coverage. Moreover, the long scan times often associated with high-resolution imaging are an additional limiting factor.</p><p><strong>Purpose: </strong>To combine calibration-free parallel transmit technology (pTx) using universal pulses (UP) with advanced imaging acceleration strategies to achieve homogenous multicontrast 7T MRI with whole-brain coverage and high spatial resolution in short scan time.</p><p><strong>Materials and methods: </strong>Ten healthy volunteers were scanned both with conventional vendor-provided sequences and with custom sequences for anatomical whole-brain imaging [-weighted, -weighted, FLAIR, and susceptibility-weighted]. The scan times for the 2 anatomical protocols were matched (25 minutes). In addition, a quantitative MRI protocol [multi-parametric mapping (MPM) and chemical exchange saturation transfer (CEST)] was scanned twice using custom sequences with conventional (circular polarized) and UPs, respectively, in a scan time of 2×25 minutes. Moreover, 4 patients with different neurological diseases were scanned, namely temporal lobe epilepsy, spinocerebellar ataxia, cerebral amyloid angiopathy, and glioblastoma. For the patients, only optimized custom sequences with UPs were acquired.</p><p><strong>Results: </strong>Compared with conventional implementations, the custom sequences provide strongly improved image homogeneity and quality with significantly higher SNR and CNR across the whole brain, including cerebellum and brain stem. Moreover, UPs improve the repeatability of derived quantitative parameters. The suggested protocol has additionally been successfully demonstrated in 4 patients with different neurological pathologies.</p><p><strong>Conclusions: </strong>Homogeneous whole-brain 7T MRI with high spatial resolution and high image quality is possible in clinically feasible scan times. The developed protocol can be applied without any expert knowledge and is ready for clinical use. The approach could largely extend applicability of UHF MRI in neuroradiology paving the way for increased routine use of 7T MRI.</p>","PeriodicalId":14486,"journal":{"name":"Investigative Radiology","volume":" ","pages":""},"PeriodicalIF":7.9,"publicationDate":"2025-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13117539/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145793821","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Discovery of Gadopiclenol: An Example of Rational Drug Design?","authors":"Marc Port","doi":"10.1097/RLI.0000000000001169","DOIUrl":"10.1097/RLI.0000000000001169","url":null,"abstract":"<p><strong>Abstract: </strong>Gadopiclenol was initially developed as a high-relaxivity, nonspecific magnetic resonance imaging contrast agent to enhance image quality and thereby improve diagnostics. This design required a highly demanding Drug Target Profile, addressing not only relaxivity but also factors such as physicochemical properties of the injectable solution (viscosity, osmolality, heat sterilization compatibility), pharmacokinetics and toxicity, particularly related to the stability of the complex. These considerations led to a multiparametric molecular design based on a gadolinium complex characterized by the following features: (1) a macrocyclic, nonionic structure based on the PCTA framework with 2 water molecules in the inner sphere; (2) the introduction of steric constraints around the gadolinium to enhance stability and reduce relaxivity quenching by endogenous ions; (3) slowed rotational diffusion due to gadolinium's position at the center of the complex; and (4) the incorporation of 3 hydrophilic amino polyol pendant arms to ensure aqueous solubility, reduce binding with endogenous proteins, and enhance product safety.This rational design led to the creation of a first prototype, P03277V1. However, the occurrence of nephrogenic systemic fibrosis necessitated modifications to the Drug Target Profile, aimed at improving the complex's stability and reducing production costs. This was achieved through the discovery of an isomerization process for P03277V1, resulting in gadopiclenol, which demonstrated excellent kinetic stability.The rational design of gadopiclenol thus exemplifies the concept of Property-Based Drug Design used in medicinal chemistry. It also highlights that the complexity of designing a diagnostic agent is comparable to that of a therapeutic agent. Furthermore, the case of gadopiclenol illustrates that the medical positioning of a drug candidate can evolve during clinical development. Gadopiclenol's medical positioning shifted from being a product with high relaxivity to improve signal strength, to one intended for use at a half dose to limit gadolinium injection and minimize risks to patients, such as nephrogenic systemic fibrosis or accumulation in specific areas of the brain. Currently, gadopiclenol is approved for clinical use at a dose of 0.05 mmol/kg to minimize gadolinium exposure to patients. Whether the 0.1 mmol/kg dose can be used to enhance clinical diagnostics and improve patient management in the future remains to be seen.</p>","PeriodicalId":14486,"journal":{"name":"Investigative Radiology","volume":" ","pages":"809-812"},"PeriodicalIF":8.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143604818","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optimized Variable Flip Angle Technique for Specific Absorption Rate Reduction in Metal Artifact Reduction Magnetic Resonance Imaging.","authors":"Iman Khodarahmi, William Walter, Paul Wojack, Mary Bruno, Jan Fritz, Mahesh B Keerthivasan","doi":"10.1097/RLI.0000000000001249","DOIUrl":"10.1097/RLI.0000000000001249","url":null,"abstract":"<p><strong>Objectives: </strong>Metal artifact reduction MRI can exceed specific absorption rate (SAR) limits due to high-bandwidth radiofrequency pulses, causing scan interruptions and prolonged acquisition times. The aim of the current study is to reduce SAR and potentially scan time in metal artifact reduction MRI using an optimized variable refocusing flip angle (VRFA) scheme compared with the standard constant refocusing flip angle (CRFA).</p><p><strong>Materials and methods: </strong>Three VRFA variants (VRFA1 to VRFA3) were developed to maximize tissue signal and contrast while minimizing SAR and image blur. The optimal variant was selected through quantification of metal artifacts and image blur in phantoms and tissue signal in a volunteer. Patients with hip arthroplasty underwent CRFA and optimal VRFA imaging using high-bandwidth turbo-spin-echo (HBW-TSE) and compressed-sensing slice-encoding-for-metal-artifact-correction (CS-SEMAC) sequences. Three readers ranked paired CRFA and VRFA scans for quality. Analyses included repeated measures ANOVA, noninferiority testing, and paired t/Wilcoxon signed-rank tests.</p><p><strong>Results: </strong>CRFA and VRFA1 to VRFA3 showed no significant differences in image blur (full-width-at-half-maximum, mean ± SD, 1.9 ± 0.2 vs 1.9 ± 0.2 vs 1.9 ± 0.3 vs 1.9 ± 0.3 pixels, P = 0.06) or metal artifacts (8.2 ± 2.8 vs 8.4 ± 2.7 vs 8.4 ± 2.6 vs 8.4 ± 2.7 pixels, P = 0.57). The optimal VRFA variant (VRFA3) preserved 81% of CRFA fat-muscle contrast at 77% SAR and 70% scan time on proton-density (PD), and 94% of fluid-muscle contrast at 80% SAR and 67% scan time on short-tau-inversion-recovery (STIR). In 23 patients [mean age, 67.3 y ± 12.2 (SD); 14 females], the optimal VRFA was noninferior to CRFA in all quality metrics (all 95% CI < noninferiority margin = 0.1) and significantly reduced SAR (mean, PD-HBW-TSE/STIR-HBW-TSE/PD-CS-SEMAC/STIR-CS-SEMAC: 1.11/1.35/1.17/1.18 vs 1.85/1.83/1.49/1.46 W/kg, all P ≤ 0.001). In HBW-TSE, reduced SAR allowed longer echo trains and 15% to 32% shorter scan times.</p><p><strong>Conclusion: </strong>Metal artifact reduction MRI with VRFA reduces SAR without compromising image quality. It allows shorter acquisitions in HBW-TSE.</p>","PeriodicalId":14486,"journal":{"name":"Investigative Radiology","volume":" ","pages":""},"PeriodicalIF":7.9,"publicationDate":"2025-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13117572/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145540680","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Contrast Agent-Specific Parameter Optimization for T 1 -Weighted Fast Spoiled Gradient Echo Imaging : Use Cases for Gadoterate Meglumine and Gadobutrol at 1.5T and 3.0T.","authors":"Dimosthenis E Gkotsis, Anand Bherwani, Eftychia Z Kapsalaki, Courtney J Bishop, Adam J Schwarz","doi":"10.1097/RLI.0000000000001205","DOIUrl":"10.1097/RLI.0000000000001205","url":null,"abstract":"<p><strong>Objectives: </strong>The objective of this study is to derive a contrast agent-specific theoretical framework to optimize acquisition parameters for contrast-enhanced magnetic resonance imaging (MRI) based on the physiochemical properties of gadolinium-based contrast agents, focusing on fast spoiled gradient recalled echo sequences. The goal is to enhance the lesion-to-background contrast for improved diagnostic sensitivity in clinical applications.</p><p><strong>Materials and methods: </strong>Signal equations for fast spoiled gradient recalled echo sequences were derived for nonenhancing and enhancing tissues using gadoterate meglumine and gadobutrol, characterized by distinct longitudinal (r 1 ) and transverse (r 2 /r* 2 ) relaxivities. Simulations were conducted at 2 field strengths, 1.5T and 3.0T, and various scenarios were considered, including hypothetical lesions with T 1 ratios ranging from 1.1 to 1.8. The signal behavior was analyzed across a range of initial conditions, including different spin densities and field-strength dependent variations in tissue relaxation times. The optimal flip angle and repetition time combinations were determined to maximize contrast. In vivo validation was performed on 2 patients undergoing contrast-enhanced MRI of the brain, using the proposed acquisition parameters.</p><p><strong>Results: </strong>The modeling and simulations revealed that the flip angle that maximizes signal intensity for a contrast-enhancing lesion (Ernst angle) differs from the flip angle that maximizes T 1 -dependent contrast between lesion and healthy tissue in unenhanced MRI (Pelc angle) and also differs from the flip angle that maximizes the same in contrast-enhanced MRI. The theoretical simulations indicated possible contrast gains of 24%-28% using optimized parameters. The in vivo acquisitions demonstrated contrast gains of 19%-44% for a diffuse enhancing lesion and 91% for a weakly enhancing focal lesion, when comparing the optimized acquisition parameters to manufacturer's default settings.</p><p><strong>Conclusions: </strong>Adjusted repetition time and flip angle values, derived using the proposed framework, improved the image contrast between healthy and diseased tissues, enhancing the visualization of abnormalities. This approach can be used to optimize routine clinical MRI protocols and balance scan time with contrast enhancement. This may translate to more precise lesion detection, potentially leading to earlier and more accurate diagnosis or treatment monitoring in clinical practice.</p>","PeriodicalId":14486,"journal":{"name":"Investigative Radiology","volume":" ","pages":"791-801"},"PeriodicalIF":8.0,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12490333/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144009759","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lesion Visualization of an Oral Manganese Contrast Agent Compared to Unenhanced MRI and Gadobenate Dimeglumine in Patients Undergoing Liver Magnetic Resonance Imaging for Evaluation of Colorectal Cancer Metastases: Centralized Assessment of a Randomized, Crossover, Phase II Study.","authors":"Torkel B Brismar, Nikolaos Kartalis, Nadilka Hettiarachchige, Andreas Norlin","doi":"10.1097/RLI.0000000000001184","DOIUrl":"10.1097/RLI.0000000000001184","url":null,"abstract":"<p><strong>Objectives: </strong>The primary objective of this study was to evaluate the visualization capability of orally administered manganese chloride tetrahydrate (ACE-MBCA [Ascelia Pharma-manganese-based contrast agent, also referred to as Orviglance or CMC-001]), a novel liver-specific contrast agent developed by Ascelia Pharma, as a liver-specific MRI contrast agent compared with that of the unenhanced MRI for focal liver lesions in a properly blinded study design. The secondary objective was to compare the performance of ACE-MBCA with gadobenate dimeglumine.</p><p><strong>Materials and methods: </strong>Three independent readers analyzed MRI examinations from a previously completed randomized crossover clinical trial in a blinded manner in a centralized setting. The study included 20 consecutive adult patients with known or suspected liver metastases, who received both ACE-MBCA and gadobenate dimeglumine. The readers evaluated 6 types of MRI scans (unenhanced, enhanced, and combined MRI for both contrast agents) with lesion visualization [lesion border delineation (LBD) and lesion contrast (LC)] as primary outcome. To maintain the blinded nature of the study, all statistical analyses were performed by an independent statistician who was not involved in the image reading process. Differences in primary outcomes were performed using 1-sided paired t tests at a significance level of 0.025 for both parameters. For secondary outcomes (ACE-MBCA enhanced MRI visualization, lesion detection, size measurements, reader confidence, quantitative parameters, and image quality were compared with that of the other scans), descriptive statistics and 95% confidence intervals were used to evaluate differences between categories in comparative analyses, without formal hypothesis testing for most secondary endpoints.</p><p><strong>Results: </strong>ACE-MBCA-enhanced MRI demonstrated statistically significant superior scoring over unenhanced MRI for visualizing focal liver lesions, with mean LBD scores improving from 1.8-2.3 to 2.4-2.9 and LC scores ranging from 1.8-2.3 to 2.8-3.3 across all 3 readers ( P  < 0.001). Compared with unenhanced MRI, ACE-MBCA detected significantly more lesions across all readers (mean differences 0.4-0.8 lesions, 95% CI: 0.04-1.52), particularly for small lesions (<1 cm), where detection improved from 2-6 to 3-12 lesions. Liver-to-lesion contrast and contrast-to-noise ratios were also significantly higher after ACE-MBCA enhancement. All visualization parameters of ACE-MBCA were comparable to those of gadobenate dimeglumine, with no significant differences.</p><p><strong>Conclusions: </strong>Compared with unenhanced MRI, ACE-MBCA MRI resulted in superior visualization and a greater number of detected liver lesions. ACE-MBCA and gadobenate dimeglumine performed similarly in the visualization and detection of colorectal liver metastases.</p>","PeriodicalId":14486,"journal":{"name":"Investigative Radiology","volume":" ","pages":"802-808"},"PeriodicalIF":8.0,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12490331/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143803287","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Overall Gadolinium Exposure Within the First 5 Months After Injection of Human Equivalent Doses of Gadopiclenol, Gadoterate, or Gadobutrol in Healthy Rats.","authors":"Marlène Rasschaert, Emilie Couloumy, Elisabeth Renard, Claire Hollenbeck, Nathalie Fretellier, Izabela Strzeminska, Ilona Janot, Mylene Lefebvre, Nathalie Decout, Cecile Factor, Philippe Robert","doi":"10.1097/RLI.0000000000001194","DOIUrl":"10.1097/RLI.0000000000001194","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;Gadopiclenol is a high relaxivity macrocyclic and nonionic Gadolinium-Based Contrast Agent (GBCA) for central nervous system (CNS) and Body MRI, approved in September 2022 by the Food and Drug Administration and in December 2023 by the European Medicine Agency and others European health authorities. Gadopiclenol is currently indicated at half gadolinium-dose (0.05 mmol/kg body weight) compared to the other nonspecific marketed GBCAs. This study aims to evaluate the impact of this gadolinium (Gd) dose reduction in terms of overall Gd body exposure. Requiring tissue samples at different times, this information is only accessible through animal experiment. In this study, the Gd exposure over a 5-month period was evaluated in healthy rats after a single injection of gadopiclenol in comparison with 2 other macrocyclic GBCAs approved for human use, gadobutrol and gadoterate, all administered at their respective human equivalent dose (HED).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Material and methods: &lt;/strong&gt;Healthy 9-week-old female Sprague-Dawley rats were randomly allocated to 4 groups, receiving 1 single intravenous injection of gadoterate (Dotarem, 0.6 mmol/kg), gadobutrol (Gadovist, 0.6 mmol/kg), gadopiclenol (Elucirem, 0.3 mmol/kg), or saline (control group). Animals were euthanized 1 day (D1), 1 week (W1), 1 month (M1), or 5 months (M5) after the injection (n = 10/group and time-point). Selected tissues (including central [CNS] and peripheric nervous system [PNS] organs, excretion organs, bone) were collected for subsequent total Gd determination with inductively coupled plasma mass spectrometry. Based on Gd concentration measurements at these different time points, the 5 months overall exposure to Gd in each organ was estimated by calculating the area under the curve (AUC), between the first and the last time point. The whole study was performed in a blinded manner.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Following gadopiclenol administration to rats at the HED, overall Gd exposure over 5 months was found to be 25% to 40% lower compared to gadoterate and gadobutrol, respectively. Organ by organ, Gd exposure reduction is observed over the studied period in the plasma, CNS (cerebellum, cortical brain, subcortical brain, brain stem, spinal cord), PNS (spinal nodes, sciatic nerve, footpads), the spleen, the skin, the liver, and the kidney. In the femur, the Gd exposure after gadopiclenol administration was higher or equivalent compared to gadobutrol and gadoterate in the mineral parts of the bone (diaphysis and epiphysis), but lower in the bone marrow. Residual Gd found in each tissue studied is extremely low relative to the injected dose), with values ranging from 10 -6 (CNS) to 10 -3 (kidney, mineral bone) % injected dose/g of organ.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;Under our experimental conditions, the overall measured Gd exposure over 5 months following gadopiclenol injection in rats at the HED is 25-40% lower than that after gadoterate a","PeriodicalId":14486,"journal":{"name":"Investigative Radiology","volume":" ","pages":"753-767"},"PeriodicalIF":8.0,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12490341/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144093391","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Safety of Gadoterate Meglumine: A Review of 35 Years of Clinical Use and More Than 170 Million Doses.","authors":"Imran Shahid, Joëlle Morvan, Elisabeth Darmon-Kern, Frantz Hebert, Eric Lancelot, Philippe Bourrinet","doi":"10.1097/RLI.0000000000001200","DOIUrl":"10.1097/RLI.0000000000001200","url":null,"abstract":"<p><strong>Aim: </strong>The aim of this review was to evaluate the safety profile of gadoterate meglumine from published literature and pharmacovigilance reports of adverse drug reactions (ADRs) encompassing 35 years of clinical use and more than 170 million administered doses.</p><p><strong>Materials and methods: </strong>A review of published literature up to December 31, 2024 was performed through a search in Embase and PubMed databases. The analysis focused on current safety concerns associated with gadolinium-based contrast agents, the hypersensitivity reactions (HSRs), nephrogenic systemic fibrosis (NSF), gadolinium accumulation, and symptoms associated with gadolinium exposure.</p><p><strong>Results: </strong>A total of 62 publications reporting safety results for gadoterate meglumine were included. Age ranged from a few weeks to 103 years, including patients with all stages of renal impairment. The incidence of HSRs was reported in 17 studies and ranged from <0.01% to 0.58%. Occurrence of NSF was analyzed in 9 studies; to date, no confirmed unconfounded case of NSF diagnosis has been associated with gadoterate meglumine use. Regarding gadolinium presence in the body, 17 studies did not show any significant signal intensity increase in the deep brain in patients after up to 53 exposures, while 4 showed some signal intensity increase in specific subgroups after repeated exposure, but without any clinical symptoms. Symptoms associated with gadolinium exposure have been described in 8 studies, although no causal relationship with gadolinium deposition was established. Safety data obtained from pharmacovigilance monitoring showed an incidence of adverse reactions in 8 cases per 100,000 patients exposed. The most frequently reported adverse reactions were urticaria, nausea, and vomiting (0.001% each), while the incidence of HSRs was less than 0.00035%. No unconfounded NSF reports were received.</p><p><strong>Conclusions: </strong>Clinical evidence from the published data and pharmacovigilance monitoring demonstrated that gadoterate meglumine is a safe magnetic resonance imaging contrast agent for all age groups in a variety of approved indications throughout the whole body, including in patients with renal impairment.</p>","PeriodicalId":14486,"journal":{"name":"Investigative Radiology","volume":" ","pages":"711-721"},"PeriodicalIF":8.0,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12490340/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143990660","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}