Investigative RadiologyPub Date : 2025-06-01Epub Date: 2024-12-24DOI: 10.1097/RLI.0000000000001139
Dominika Skwierawska, Sebastian Bickelhaupt, Maximilian Bachl, Rolf Janka, Martina Murr, Felix Gloger, Tristan A Kuder, Moritz Zaiss, Dominique Hadler, Michael Uder, Frederik B Laun
{"title":"Relevance of Prostatic Fluid on the Apparent Diffusion Coefficient: An Inversion Recovery Diffusion-Weighted Imaging Investigation.","authors":"Dominika Skwierawska, Sebastian Bickelhaupt, Maximilian Bachl, Rolf Janka, Martina Murr, Felix Gloger, Tristan A Kuder, Moritz Zaiss, Dominique Hadler, Michael Uder, Frederik B Laun","doi":"10.1097/RLI.0000000000001139","DOIUrl":"10.1097/RLI.0000000000001139","url":null,"abstract":"<p><strong>Objectives: </strong>Diffusion-weighted imaging (DWI) is pivotal for prostate magnetic resonance imaging. This is rooted in the generally reduced apparent diffusion coefficient (ADC) observed in prostate cancer in comparison to healthy prostate tissue. This difference originates from microstructural tissue composition changes, including a potentially decreased fluid-containing lumen volume. This study explored the nature of the observed ADC contrast in prostate tissue through inversion recovery-prepared DWI examinations that generated varying levels of fluid suppression.</p><p><strong>Materials and methods: </strong>This institutional review board-approved, single-center, prospective study was conducted from 2023 to 2024; all participants underwent magnetic resonance imaging including DWI with b-values of 50 and 800 s/mm 2 at 16 inversion times (TI; 60-4000 milliseconds). The measured ADC was interpreted with a 2-compartment model (compartments: tissue and fluid). Descriptive statistics were computed for all analyzed parameters.</p><p><strong>Results: </strong>Twelve healthy male volunteers (45 ± 17 years) and 1 patient with prostate adenocarcinoma (66 years) were evaluated. The ADC map appearance depended heavily on the TI, and we observed a feature-rich ADC(TI) curve. The ADC in the transition zone (TZ) of healthy volunteers increased between TI = 60 milliseconds and approximately 1100 milliseconds, then dropped drastically before increasing again, stabilizing at a very high TI. This effect was greatly reduced in the patient's prostate cancer lesion. The 2-compartment model described this behavior well. After the inversion, tissue magnetization recovers faster, decreasing its signal contribution in absolute terms and resulting in an increase in the ADC. At the tipping point, the total magnetization is zero at b = 0, when the positive tissue magnetization and still-inverted fluid magnetization cancel out. A small diffusion encoding leads to a positive signal, thus generating an infinite ADC. After the tipping point, the fluid magnetization remains negative and thereby reduces the ADC.</p><p><strong>Conclusions: </strong>Prostate fluid appears to contribute significantly to prostate ADCs. Its contribution could be adjusted by choosing an appropriate inversion recovery preparation, potentially enhancing contrast for prostate cancer lesions.</p>","PeriodicalId":14486,"journal":{"name":"Investigative Radiology","volume":" ","pages":"357-368"},"PeriodicalIF":7.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142768861","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}
Investigative RadiologyPub Date : 2025-06-01Epub Date: 2024-12-13DOI: 10.1097/RLI.0000000000001142
Carlos Bilreiro, Francisca F Fernandes, Rui V Simões, Rafael Henriques, Cristina Chavarrías, Andrada Ianus, Mireia Castillo-Martin, Tânia Carvalho, Celso Matos, Noam Shemesh
{"title":"Pancreatic Intraepithelial Neoplasia Revealed by Diffusion-Tensor MRI.","authors":"Carlos Bilreiro, Francisca F Fernandes, Rui V Simões, Rafael Henriques, Cristina Chavarrías, Andrada Ianus, Mireia Castillo-Martin, Tânia Carvalho, Celso Matos, Noam Shemesh","doi":"10.1097/RLI.0000000000001142","DOIUrl":"10.1097/RLI.0000000000001142","url":null,"abstract":"<p><strong>Objectives: </strong>Detecting premalignant lesions for pancreatic ductal adenocarcinoma, mainly pancreatic intraepithelial neoplasia (PanIN), is critical for early diagnosis and for understanding PanIN biology. Based on PanIN's histology, we hypothesized that diffusion tensor imaging (DTI) and T2* could detect PanIN.</p><p><strong>Materials and methods: </strong>DTI was explored for the detection and characterization of PanIN in genetically engineered mice (KC, KPC). Following in vivo DTI, ex vivo ultrahigh-field (16.4 T) MR microscopy using DTI, T2* was performed with histological validation. Sources of MR contrasts and histological features were investigated, including histological scoring for disease burden (lesion span) and severity (adjusted score). To test if findings in mice can be translated to humans, human pancreas specimens were imaged.</p><p><strong>Results: </strong>DTI detected PanIN and pancreatic ductal adenocarcinoma in vivo (6 KPC, 4 KC, 6 controls) with high discriminative ability: fractional anisotropy (FA) and radial diffusivity with area under the curve = 0.983 (95% confidence interval: 0.932-1.000); mean diffusivity and axial diffusivity (AD) with area under the curve = 1 (95% confidence interval: 1.000-1.000). MR microscopy with histological correlation (20 KC/KPC; 5 controls) revealed that sources of MR contrasts likely arise from microarchitectural signatures: high FA, AD in fibrotic areas surrounding lesions, high diffusivities within cysts, and high T2* within lesions' stroma. The strongest histological correlations for lesion span and adjusted score were obtained with AD ( R = 0.708, P < 0.001; R = 0.789, P < 0.001, respectively). Ex vivo observations in 5 human pancreases matched our findings in mice, revealing substantial contrast between PanIN and normal pancreas.</p><p><strong>Conclusions: </strong>DTI and T2* are useful for detecting and characterizing PanIN in genetically engineered mice and in the human pancreas, especially with AD and FA. These are encouraging findings for future clinical applications of pancreatic imaging.</p>","PeriodicalId":14486,"journal":{"name":"Investigative Radiology","volume":" ","pages":"397-406"},"PeriodicalIF":7.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142818167","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}
Investigative RadiologyPub Date : 2025-06-01Epub Date: 2024-11-28DOI: 10.1097/RLI.0000000000001141
Byungjin Choi, Subin Heo, Jennifer S Mcdonald, Sang Hyun Choi, Won-Mook Choi, Jung Bok Lee, Eunyoung Angela Lee, Seong Ho Park, Soobeen Seol, Sujin Gan, Bumhee Park, Hee Jung Choi, Byoung Je Kim, Sang Youl Rhee, Seung Baek Hong, Kyung-Hee Kim, Young Hwan Lee, Seung Soo Kim, Rae Woong Park
{"title":"Risk of Contrast-Induced Acute Kidney Injury in Computed Tomography: A 16 Institutional Retrospective Cohort Study.","authors":"Byungjin Choi, Subin Heo, Jennifer S Mcdonald, Sang Hyun Choi, Won-Mook Choi, Jung Bok Lee, Eunyoung Angela Lee, Seong Ho Park, Soobeen Seol, Sujin Gan, Bumhee Park, Hee Jung Choi, Byoung Je Kim, Sang Youl Rhee, Seung Baek Hong, Kyung-Hee Kim, Young Hwan Lee, Seung Soo Kim, Rae Woong Park","doi":"10.1097/RLI.0000000000001141","DOIUrl":"10.1097/RLI.0000000000001141","url":null,"abstract":"<p><strong>Objectives: </strong>Concern about contrast-induced acute kidney injury (CI-AKI) may delay the timely administration of contrast media for computed tomography (CT). The precise causative effect of iodinated contrast media on CI-AKI and its relevant risk factors remains an area of ongoing investigation. Therefore, this study aimed to determine the risk of CI-AKI following contrast-enhanced CT and its predisposing risk factors.</p><p><strong>Materials and methods: </strong>This study employed a 1:1 propensity score matching analysis using electronic medical records gathered between January 2006 and December 2022 from 16 institutions in South Korea. Contrast-enhanced and nonenhanced CT scans in patients aged 18 years and above were matched for baseline estimated glomerular filtration rate (eGFR), demographic characteristics, and clinical variables to assess the risk of CI-AKI. Subgroup analyses were conducted to evaluate any significant risk factors for CI-AKI.</p><p><strong>Results: </strong>A total of 182,170 CT scans with contrast were matched to 182,170 CT scans without contrast. The risk of CI-AKI in the entire study cohort was not statistically significant (odds ratio [OR], 1.036; 95% confidence interval [CI], 0.968-1.109; P = 0.34). Subgroup analyses revealed a significantly higher risk of CI-AKI in patients with eGFR <30 mL/min/1.73m 2 (OR, 1.176; 95% CI, 1.080-1.281; P = 0.011) or eGFR 30-45 mL/min/1.73m 2 (OR, 1.139; 95% CI, 1.043-1.244; P = 0.019), patients diagnosed with chronic kidney disease (OR, 1.215; 95% CI, 1.084-1.361; P = 0.011), and those administered with iso-osmolar contrast media (OR, 1.392; 95% CI, 1.196-1.622; P = 0.011).</p><p><strong>Conclusions: </strong>The risk of CI-AKI following CT was minimal in the general population. However, caution is warranted for patients with chronic kidney disease and eGFR lower than 45 mL/min/1.73m 2 , or those administered with iso-osmolar contrast media.</p>","PeriodicalId":14486,"journal":{"name":"Investigative Radiology","volume":" ","pages":"376-386"},"PeriodicalIF":7.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142739365","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}
Investigative RadiologyPub Date : 2025-06-01Epub Date: 2024-12-02DOI: 10.1097/RLI.0000000000001138
Paola Clauser, Nina Pötsch, Ambra Santonocito, Francesca Ferrara, Layla Zeitouni, Mathias Hörnig, Michael Weber, Pascal A T Baltzer, Thomas H Helbich
{"title":"Contrast-Enhanced Digital Breast Tomosynthesis Compared With Contrast-Enhanced Mammography and Magnetic Resonance Imaging in the Assessment of Breast Lesions: A Pilot Study.","authors":"Paola Clauser, Nina Pötsch, Ambra Santonocito, Francesca Ferrara, Layla Zeitouni, Mathias Hörnig, Michael Weber, Pascal A T Baltzer, Thomas H Helbich","doi":"10.1097/RLI.0000000000001138","DOIUrl":"10.1097/RLI.0000000000001138","url":null,"abstract":"<p><strong>Objectives: </strong>Contrast-enhanced mammography (CEM) is an accurate competitor for contrast-enhanced breast magnetic resonance imaging (CE-MRI), but the examination is limited by the lack of 3D information. Digital breast tomosynthesis (DBT) allows better lesion detection and characterization compared with mammography. The availability of quasi-3D contrast imaging could further improve the performance of CEM. The aim of our analysis was to compare the diagnostic performance of a contrast-enhanced digital breast tomosynthesis prototype (CE-DBTp) to CEM and to CE-MRI.</p><p><strong>Materials and methods: </strong>This prospective study was approved by the ethics committee, and all patients gave written informed consent. Women who presented with suspicious findings on mammography, DBT, or ultrasound were invited to participate in the study. Participants underwent CEM and CE-DBTp of the breast with the suspicious findings as well as bilateral CE-MRI. Histology was used as the standard of reference. Four readers (R1 and R2 non-experienced; R3 and R4 experienced) evaluated the images, blinded to patients' history, previous imaging, and histology. The readers evaluated CEM, CE-DBTp, and CE-MRI in separate sessions and gave a BI-RADS score for each finding. Sensitivity, specificity, lesion conspicuity, and readers' confidence were calculated and compared.</p><p><strong>Results: </strong>We included 84 patients (mean age, 56 years; range, 39-70) with 91 histologically verified breast lesions (27 benign, 64 malignant). The accuracy of the CE-DBTp was high, but significant differences were seen between experienced (both 86.8%) and non-experienced readers (76.9% and 78%, P = 0.021). No differences were found between CEM and CE-DBTp, whereas the accuracy of CE-MRI was higher ( P = 0.002). Sensitivity with CE-DBTp varied (89.1% to 100%) between experienced and non-experienced readers ( P = 0.074), and it was comparable to CEM but lower than CE-MRI ( P = 0.003). Specificity was variable between readers with all modalities. Lesion conspicuity was higher for the CE-DBTp and CE-MRI than for CEM, and confidence was significantly higher with the CE-DBTp than with CEM for one of the readers ( P < 0.001).</p><p><strong>Conclusions: </strong>A high sensitivity and good accuracy were achieved with the CE-DBTp. Lesion conspicuity and readers' confidence were higher with the CE-DBTp compared with CEM. However, CE-MRI had the highest sensitivity and accuracy.</p>","PeriodicalId":14486,"journal":{"name":"Investigative Radiology","volume":" ","pages":"369-375"},"PeriodicalIF":7.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142768857","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":"Improved MR Detection of Optic Nerve Demyelination With MP2RAGE-FLAWS Compared With T 2 -Weighted Fat-Saturated Sequences.","authors":"Randa Aichour, Thibaut Emorine, Nadia Oubaya, Imen Megdiche, Alain Créange, Augustin Lecler, Tobias Kober, Aurélien Massire, Blanche Bapst","doi":"10.1097/RLI.0000000000001140","DOIUrl":"10.1097/RLI.0000000000001140","url":null,"abstract":"<p><strong>Objectives: </strong>Nonenhanced T 1 -w sequences such as magnetization-prepared 2 rapid acquisition gradient echo (MP2RAGE) and derived fluid and white matter suppression (FLAWS) have demonstrated high performance for detecting brain parenchymal and cervical spine demyelinating lesions in multiple sclerosis. However, their potential for identifying optic nerve (ON) demyelination remains unexplored. The aim of this study was to evaluate the performance of compressed sensing-accelerated (CS) MP2RAGE-FLAWS imaging for detection of ON demyelination lesions compared with T2-w fat-saturated (FS) TSE imaging in a clinical setting.</p><p><strong>Materials and methods: </strong>We conducted a retrospective study of magnetic resonance scans acquired on patients with central nervous system demyelinating disorders between January and December 2022. Inclusion criteria were the acquisition in the same session of a brain CS-MP2RAGE-FLAWS imaging and a combination of axial + coronal T2-w FS orbital sequences. A 4-step radiological analysis-including blinded and consensus readings-assessed ON lesion detection. The reference standard was the final reading session of radiologists using the entire patient file. Sensitivities and specificities of both sequences were computed and compared using McNemar χ 2 tests.</p><p><strong>Results: </strong>Thirty-nine patients (mean age: 43 ± 14 years; 25 women) were analyzed, including 34 with multiple sclerosis, 2 with MOGAD (myelin oligodendrocyte glycoprotein antibody-associated disease), 1 with NMOSD (neuromyelitis optica spectrum disorder), and 2 with indeterminate demyelinating disease. Among the 78 ONs analyzed, 64 lesions were detected with CS-MP2RAGE-FLAWS as opposed to 37 with 2D T2-w FS imaging, corresponding to a total of 41 and 27 affected nerves, respectively. CS-MP2RAGE-FLAWS exhibited higher sensitivity for overall detection of ON lesions compared with 2D T2-w FS imaging (97.5% vs 67.5%, P = 0.001) without reducing the specificity. Improved lesion detectability with CS-MP2RAGE-FLAWS was significant compared with 2D T2-w FS in intraorbital and intracanalicular segments (respectively, 92.3% vs 50% and 96.3% vs 66.7%; P < 0.05). There was no difference in sensitivity ( P = 0.69) or specificity ( P = 0.99) regarding the intracranial segment analysis.</p><p><strong>Conclusions: </strong>CS-MP2RAGE-FLAWS sequence improves ON lesion detection compared with conventional 2D T2-w FS, especially in the intraorbital segment, while simultaneously providing whole-brain and cervical spinal cord imaging at no additional time cost.</p>","PeriodicalId":14486,"journal":{"name":"Investigative Radiology","volume":" ","pages":"387-396"},"PeriodicalIF":7.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142739363","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}
Investigative RadiologyPub Date : 2025-06-01Epub Date: 2024-12-09DOI: 10.1097/RLI.0000000000001145
Kianush Karimian-Jazi, Noah Enbergs, Evgeny Golubtsov, Katharina Schregel, Johannes Ungermann, Hannah Fels-Palesandro, Daniel Schwarz, Volker Sturm, Julius M Kernbach, David Batra, Franziska M Ippen, Irada Pflüger, Nikolaus von Knebel Doeberitz, Sabine Heiland, Lukas Bunse, Michael Platten, Frank Winkler, Wolfgang Wick, Daniel Paech, Martin Bendszus, Michael O Breckwoldt
{"title":"Differentiating Glioma Recurrence and Pseudoprogression by APTw CEST MRI.","authors":"Kianush Karimian-Jazi, Noah Enbergs, Evgeny Golubtsov, Katharina Schregel, Johannes Ungermann, Hannah Fels-Palesandro, Daniel Schwarz, Volker Sturm, Julius M Kernbach, David Batra, Franziska M Ippen, Irada Pflüger, Nikolaus von Knebel Doeberitz, Sabine Heiland, Lukas Bunse, Michael Platten, Frank Winkler, Wolfgang Wick, Daniel Paech, Martin Bendszus, Michael O Breckwoldt","doi":"10.1097/RLI.0000000000001145","DOIUrl":"10.1097/RLI.0000000000001145","url":null,"abstract":"<p><strong>Objectives: </strong>Recurrent glioma is highly treatment resistant due to its metabolic, cellular, and molecular heterogeneity and invasiveness. Tumor monitoring by conventional MRI has shortcomings to assess these key glioma characteristics. Recent studies introduced chemical exchange saturation transfer for metabolic imaging in oncology and assessed its diagnostic value for newly diagnosed glioma. This prospective study investigates amide proton transfer-weighted (APTw) MRI at 3 T as an imaging biomarker to elucidate the molecular heterogeneity and invasion patterns of recurrent glioma in comparison to pseudoprogression (PsPD).</p><p><strong>Materials and methods: </strong>We performed a monocenter, prospective trial and screened 371 glioma patients who received tumor monitoring between August 2021 and March 2024 at our institution. The study included IDH wildtype astrocytoma and IDH mutant astrocytoma and oligodendroglioma, graded according to the WHO 2021 classification. Patients had received clinical standard of care treatment including surgical resection and radiochemotherapy prior to study inclusion. Patients were monitored by 3 monthly MRI follow-up imaging, and response assessment was performed according to the RANO criteria. Within this cohort, we identified 30 patients who presented with recurrent glioma and 12 patients with PsPD. In addition to standard anatomical sequences (FLAIR and T1-w Gd-enhanced sequences), MRI included APTw imaging. After sequence co-registration, semiautomated segmentation was performed of the FLAIR lesion, CE lesion, resection cavity, and the contralateral normal-appearing white matter, and APTw signals were quantified in these regions of interest.</p><p><strong>Results: </strong>APTw values were highest in solid, Gd-enhancing tumor parts as compared with the nonenhancing FLAIR lesion (APTw: 1.99% vs 1.36%, P = 0.001), whereas there were no detectable APTw alterations in the normal-appearing white matter (APTw: 0.005%, P < 0.001 compared with FLAIR). Patients with progressive disease had higher APTw levels compared with patients with PsPD (APTw: 1.99% vs 1.26%, P = 0.008). Chemical exchange saturation transfer identified heterogeneity within the FLAIR lesion that was not detectable by conventional sequences. There were also focal APTw signal peaks within contrast enhancing lesions as putative metabolic hotspots within recurrent glioma. The resection cavity developed an APTw increase at recurrence that was not detectable prior to recurrence nor in patients with PsPD (APTw before recurrence: 0.6% vs 2.68% at recurrence, P = 0.03).</p><p><strong>Conclusions: </strong>Our study shows that APTw imaging can differentiate PD and PsPD. We identify previously undetectable imaging patterns during glioma recurrence, which include alterations within resection cavity associated with disease progression. Our work highlights the clinical potential of APTw imaging for glioma monitoring and further establishes it ","PeriodicalId":14486,"journal":{"name":"Investigative Radiology","volume":" ","pages":"414-422"},"PeriodicalIF":7.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142791749","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}
Investigative RadiologyPub Date : 2025-06-01Epub Date: 2024-11-21DOI: 10.1097/RLI.0000000000001144
Alberto Spinazzi, Eric Lancelot, Letizia Vitali, Christophe Cot, Gianpaolo Pirovano, Alvin Joseph, Miles A Kirchin, Elisabeth Darmon-Kern, Philippe Bourrinet
{"title":"Safety of Gadopiclenol After Its First Year of Clinical Use.","authors":"Alberto Spinazzi, Eric Lancelot, Letizia Vitali, Christophe Cot, Gianpaolo Pirovano, Alvin Joseph, Miles A Kirchin, Elisabeth Darmon-Kern, Philippe Bourrinet","doi":"10.1097/RLI.0000000000001144","DOIUrl":"10.1097/RLI.0000000000001144","url":null,"abstract":"<p><strong>Abstract: </strong>Gadopiclenol is a novel, macrocyclic high-relaxivity gadolinium-based contrast agent recently approved for use in magnetic resonance imaging of the central nervous system and body organs at a dose of 0.05 mmol/kg body weight. Postmarketing surveillance of its first year of clinical use in the United States of America showed no serious adverse events (AEs) following over 882,550 administrations and a very low rate of nonserious AEs (1 case every 27,580 exposures). The types of observed AEs were similar to those reported for other gadolinium-based contrast agents in clinical use. Safety data from postmarketing surveillance of gadopiclenol further confirm its positive benefit-risk profile demonstrated in preapproval clinical studies.</p>","PeriodicalId":14486,"journal":{"name":"Investigative Radiology","volume":" ","pages":"423-427"},"PeriodicalIF":7.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142846440","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}
Investigative RadiologyPub Date : 2025-06-01Epub Date: 2024-11-29DOI: 10.1097/RLI.0000000000001143
Jinwei Qi, Junlin Chen, Saskia von Stillfried, Patrick Kozcera, Yang Shi, Anne Rix, Fabian Kiessling
{"title":"Molecular Ultrasound Imaging With Clinically Translatable cRGD-Coated Microbubbles to Assess α v β 3 -Integrin Expression in Inflammatory Bowel Disease.","authors":"Jinwei Qi, Junlin Chen, Saskia von Stillfried, Patrick Kozcera, Yang Shi, Anne Rix, Fabian Kiessling","doi":"10.1097/RLI.0000000000001143","DOIUrl":"10.1097/RLI.0000000000001143","url":null,"abstract":"<p><strong>Objectives: </strong>Inflammatory bowel disease (IBD) subdivides into Crohn disease (CD) and ulcerative colitis (UC), and is characterized by unpredictable periods of inflammation and results in significant patient suffering and even death. Conventional diagnostic methods, for example, colonoscopy, computed tomography, or magnetic resonance imaging, have limitations such as invasiveness, patient discomfort, and limited sensitivity and accuracy. Therefore, we propose ultrasound molecular imaging (USMI) to detect and characterize IBD. First, we evaluated integrin-α v β 3 as a biomarker of IBD in human samples and then used clinically translatable cyclic Arg-Gly-Asp-D-Phe-Lys (cRGDfK)-coupled poly(butyl)cyanoacrylate microbubbles (cRGD-MB) to assess IBD in mice.</p><p><strong>Materials and methods: </strong>Vascular integrin-α v β 3 expression in human colon tissue samples (healthy, CD and UC, n = 10 per group) was analyzed by immunofluorescence staining. In mice, acute colitis was induced by administration of 4% dextran sodium sulfate in drinking water for 5 days. On day 7, USMI with cRGD-MB was performed in colitis (n = 6) and healthy (n = 5) mice. The signal of bound cRGD-MB was assessed by the destruction-replenishment method. Ex vivo analysis of mouse colon tissue was performed to assess the degree of colitis by hematoxylin-eosin staining and the vascular expression of integrin-α v by immunofluorescence.</p><p><strong>Results: </strong>Human samples showed a significantly higher vascular integrin-α v β 3 expression in CD and UC tissue, when compared with healthy samples ( P < 0.005). In mice, a higher binding of cRGD-MB to inflamed colon was detected by USMI compared with healthy controls ( P < 0.005). Immunofluorescence staining confirmed these findings, showing stronger integrin-α v expression in acute colitis, with a good correlation between USMI signal intensity and integrin-α v expression ( r = 0.8, P = 0.0016).</p><p><strong>Conclusions: </strong>Integrin-α v β 3 on vessels is a suitable marker for IBD. USMI using cRGD-MB accurately detects this marker and correlates well with histology. These encouraging results support clinical translation of this imaging method as a noninvasive and cost-effective monitoring tool.</p>","PeriodicalId":14486,"journal":{"name":"Investigative Radiology","volume":" ","pages":"407-413"},"PeriodicalIF":7.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142750691","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}
Marlène Rasschaert, Emilie Couloumy, Elisabeth Renard, Claire Hollenbeck, Nathalie Fretellier, Izabela Strzeminska, Ilona Janot, Mylene Lefebvre, Nathalie Decout, Cecile Factor, Philippe Robert
{"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":"https://doi.org/10.1097/RLI.0000000000001194","url":null,"abstract":"<p><strong>Introduction: </strong>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).</p><p><strong>Material and methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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":""},"PeriodicalIF":7.0,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Stephan Gruendemann, Thomas Frenzel, Jessica Lohrke, Janina Boyken, Gregor Jost, Markus Berger, Hannes-Friedrich Ulbrich, Hubertus Pietsch
{"title":"In Vitro and In Vivo Stability Assessment of the Novel, Macrocyclic Gadolinium-Based Contrast Agent Gadoquatrane.","authors":"Stephan Gruendemann, Thomas Frenzel, Jessica Lohrke, Janina Boyken, Gregor Jost, Markus Berger, Hannes-Friedrich Ulbrich, Hubertus Pietsch","doi":"10.1097/RLI.0000000000001195","DOIUrl":"https://doi.org/10.1097/RLI.0000000000001195","url":null,"abstract":"<p><strong>Objectives: </strong>Gadoquatrane is a tetrameric extracellular gadolinium-based contrast agent (GBCA) with a T1 relaxivity of 11.8 L/(mmol Gd*s) at 1.41 T in human plasma, which is currently in Phase 3 clinical development. In the current study, the stability of gadoquatrane was assessed in comparison with approved macrocyclic GBCAs in several in vitro and in vivo assays.</p><p><strong>Materials and methods: </strong>Kinetic inertness, a key determinant of complex stability, was assessed for gadoquatrane, gadoteridol, gadobutrol, gadoterate, and gadopiclenol at equimolar Gd concentrations by measuring the time course of dissociation at pH 1.2 and 37°C using a complexometric assay. Kinetic inertness was also determined in human plasma at pH 7.4 and 37°C using ion exchange chromatography coupled to inductively coupled plasma mass spectrometry (ICP-MS). The binding of gadoquatrane, gadobutrol, and gadopiclenol to synthetic hydroxyapatite, the inorganic component of bone, was investigated in vitro and the Gd content in histological bone slices 1 week after a single injection of these 3 selected GBCAs in rats (0.6 mmol Gd/kg, equivalent to a human dose of 0.1 mmol Gd/kg) was analyzed using laser ablation coupled to ICP-MS.</p><p><strong>Results: </strong>The dissociation half-lives at pH 1.2 (mean, 95% confidence interval in parenthesis) were 28.6 (28.1, 29.1) days for gadoquatrane, 14.2 (13.8, 14.6) days for gadopiclenol, 2.7 (2.6, 2.8) days for gadoterate, 14.1 (13.1, 15.1) hours for gadobutrol, and 2.2 (2.0, 2.4) hours for gadoteridol. After 15 days of incubation in human plasma at pH 7.4, no released Gd3+ ions above the lower limit of quantification (LLOQ, 0.01% of total Gd) were observed for gadoquatrane and gadoterate, while for gadobutrol, gadopiclenol and gadoteridol the concentrations of released Gd3+ ions reached 0.12 (0.11, 0.13)%, 0.20 (0.19, 0.21)%, and 0.20 (0.20, 0.21)%, respectively. The rates of dissociation for gadopiclenol and gadoteridol were similar. For gadoquatrane, gadobutrol, and gadopiclenol, the binding to hydroxyapatite was examined. It was very low (< 0.02% of total Gd) for all 3 GBCAs. The Gd concentration 1 week after the injection of 0.6 mmol Gd/kg of the 3 GBCAs in bone marrow were in a comparable range of 2.3-3.0 nmol Gd/g tissue. In the epiphysis the Gd concentrations for gadoquatrane (1.2 (1.0, 1.4)) and gadobutrol (1.2 (1.0, 1.4)) were lower compared to gadopiclenol (2.2 (1.9, 2.6)). In the diaphysis the respective values were 0.5 (0.4, 0.7) nmol Gd/g, 1.0 (0.8, 1.3) nmol Gd/g, and 2.7 (2.1, 3.5) nmol Gd/g. Elemental imaging of the femur obtained in this in vivo study revealed no Gd containing structures in the mineralized bone for gadoquatrane (< 1 nmol Gd/g). For gadopiclenol, a visible thin layer of Gd concentration (interquartile range [IQR]: 17-38 nmol Gd/g, maximum value ~80 nmol Gd/g) in the subcortical layer of the bone was observed. The same layer contained a lower Gd concentration for gadobutr","PeriodicalId":14486,"journal":{"name":"Investigative Radiology","volume":" ","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144005062","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}