Determination of the MRI contrast agent concentration time course in vivo following bolus injection: Effect of equilibrium transcytolemmal water exchange

Landis, Charles; Li, Xin; Telang, Frank; Coderre, Jeffrey A.; Micca, Peggy L.; Rooney, William D.; Latour, Lawrence L.; Vétek, Gábor; Pályka, Ildikó; Springer, Charles S.

doi:10.1002/1522-2594(200010)44:4<563::aid-mrm10>3.0.co;2-#

Cited by 201 publications

(303 citation statements)

References 32 publications

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“…The SM assumes that the equilibrium water intercompartmental exchange systems remain in the FXL: it is FXLconstrained (FXL-c). We also used the FXR-and SXR-allowed (FXR-a and SXR-a) versions of the first-generation ShutterSpeed Model (SSM1), BOLus Enhanced Relaxation Overview (BOLERO) (8,11). In the SM analyses, the parameters varied are K trans and v e , while the i value is (implicitly) zero (11,13,14).…”

Section: Resultsmentioning

confidence: 99%

“…This corollary is not valid (2,6), and its assumption can effectively short circuit MRI determination of CR compartmentalization (2, 7)-the pharmacokinetic essence. In a series of papers (2,5,6,(8)(9)(10)(11)(12)(13)(14)(15)(16), we have examined the significance of this implication. We refer to models incorporating equilibrium exchange effects in the pharmacokinetic derivation as belonging to the shutter-speed model (SSM) family.…”

Section: Dynamic Nuclear Magnetic Resonance (Dnmr)mentioning

confidence: 99%

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Dynamic NMR effects in breast cancer dynamic-contrast-enhanced MRI

Huang

Morris

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

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147

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The passage of a vascular-injected paramagnetic contrast reagent (CR) bolus through a region-of-interest affects tissue 1 H2O relaxation and thus MR image intensity. For longitudinal relaxation [R1 ϵ (T1) ؊1 ], the CR must have transient molecular interactions with water. Because the CR and water molecules are never uniformly distributed in the histological-scale tissue compartments, the kinetics of equilibrium water compartmental interchange are competitive. In particular, the condition of the equilibrium transcytolemmal water exchange NMR system sorties through different domains as the interstitial CR concentration, [CRo], waxes and wanes. Before CR, the system is in the fast-exchange-limit (FXL). Very soon after CRo arrival, it enters the fast-exchange-regime (FXR). Near maximal [CRo], the system could enter even the slowexchange-regime (SXR). These conditions are defined herein, and a comprehensive description of how they affect quantitative pharmacokinetic analyses is presented. Data are analyzed from a population of 22 patients initially screened suspicious for breast cancer. After participating in our study, the subjects underwent biopsy/pathology procedures and only 7 (32%) were found to have malignancies. The transient departure from FXL to FXR (and apparently not SXR) is significant in only the malignant tumors, presumably because of angiogenic capillary leakiness. Thus, if accepted, this analysis would have prevented the 68% of the biopsies that proved benign.water exchange ͉ screening ͉ shutter speed

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Section: Resultsmentioning

confidence: 99%

Section: Dynamic Nuclear Magnetic Resonance (Dnmr)mentioning

confidence: 99%

Dynamic NMR effects in breast cancer dynamic-contrast-enhanced MRI

Huang

Morris

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

147

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“…The MRI signal was calibrated in terms of the concentration expressed in mmol/L of the CA and determined using a preprocedure T 1 map. 25,26 We had previously determined the relaxivity of the CAs in a saline solution using the 7-T small animal MRI scanner, which were 3.6 and 8.74/(mM s) for Magnevist and Gadomer, respectively. The contrast agent concentration calculations were validated by supplementary experiments.…”

Section: Dynamic Contrast Enhanced-magnetic Resonance Imagingmentioning

confidence: 99%

Impact of Drug Size on Brain Tumor and Brain Parenchyma Delivery after a Blood–Brain Barrier Disruption

Blanchette

Tremblay

Lepage

et al. 2014

J Cereb Blood Flow Metab

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Drug delivery to the brain is influenced by the blood-brain barrier (BBB) and blood-tumor barrier (BTB) to an extent that is still debated in neuro-oncology. In this paper, we studied the delivery across the BTB and the BBB of compounds with different molecular sizes in normal and glioma-bearing rats. Studies were performed at baseline as well as after an osmotic BBB disruption (BBBD) using dynamic contrast-enhanced magnetic resonance imaging and two T 1 contrast agents (CAs), Magnevist (743 Da) and Gadomer (17,000 Da). More specifically, we determined the time window for the BBB permeability, the distribution and we calculated the brain exposure to the CAs. A different pattern of accumulation and distribution at baseline as well as after a BBBD procedure was observed for both agents, which is consistent with their different molecular size and weight. Baseline tumor exposure was threefold higher for Magnevist compared with Gadomer, whereas postBBBD tumor exposure was twofold higher for Magnevist. Our study clearly showed that the time window and the extent of delivery across the intact, as well as permeabilized BTB and BBB are influenced by drug size.

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“…In this equation it is assumed that the relaxivity of the contrast agent is the same in blood and tumor, and that the exchanges of water between intravascular, extravascular, and intracellular spaces are fast (26). Three kinetic models of increasing complexity (27) were used in our study.…”

Section: Image Analysismentioning

confidence: 99%

Transvascular and interstitial transport in rat hepatocellular carcinomas: Dynamic contrast‐enhanced MRI assessment with low‐ and high‐molecular weight agents

Michoux

Huwart

Abarca‐Quinones

et al. 2008

Magnetic Resonance Imaging

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Purpose:To assess which MRI-derived kinetic parameters reflect decreased transvascular and interstitial transport when low-and high-molecular-weight agents are used in rat hepatocellular carcinomas. Materials and Methods:Dynamic MRI after injection of a low-molecular-weight contrast agent of 0.56 kDa (Gd-DOTA, gadoterate) and two high-molecular-weight contrast agents of 6.47 kDa (P792, gadomelitol) and 52 kDa (P717, carboxymethyldextran Gd-DOTA) was performed in rats with chemically induced hepatocellular carcinomas. The data were analyzed with the Kety compartmental model, the extended Kety compartmental model in which it is assumed that the tissue voxels contain a vascular component, and the St Lawrence and Lee distributed-parameter model. Results:The extravascular extracellular space accessible to the contrast agent v e and the extraction fraction E decreased with increasing molecular weight of the contrast agent. In contrast, the volume transfer constant Ktrans did not differ significantly when low-or high-molecular-weight agents were used. Conclusion:In this animal model the results suggest that the accessible extravascular extracellular space and the extraction fraction are more sensitive indicators of decreased transvascular and interstitial transport with highmolecular-weight agents than the volume transfer constant, which is a lumped representation of blood flow and permeability.

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Determination of the MRI contrast agent concentration time course in vivo following bolus injection: Effect of equilibrium transcytolemmal water exchange

Cited by 201 publications

References 32 publications

Dynamic NMR effects in breast cancer dynamic-contrast-enhanced MRI

Dynamic NMR effects in breast cancer dynamic-contrast-enhanced MRI

Impact of Drug Size on Brain Tumor and Brain Parenchyma Delivery after a Blood–Brain Barrier Disruption

Transvascular and interstitial transport in rat hepatocellular carcinomas: Dynamic contrast‐enhanced MRI assessment with low‐ and high‐molecular weight agents

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