Shelton D Caruthers

Government of Ontario, Canada, XIA, Ontario, Canada

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Publications (149)606.74 Total impact

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    [Show abstract] [Hide abstract] ABSTRACT: The research roots of (19)fluorine ((19)F) magnetic resonance imaging (MRI) date back over 35 years. Over that time span, (1)H imaging flourished and was adopted worldwide with an endless array of applications and imaging approaches, making magnetic resonance an indispensable pillar of biomedical diagnostic imaging. For many years during this timeframe, (19)F imaging research continued at a slow pace as the various attributes of the technique were explored. However, over the last decade and particularly the last several years, the pace and clinical relevance of (19)F imaging has exploded. In part, this is due to advances in MRI instrumentation, (19)F/(1)H coil designs, and ultrafast pulse sequence development for both preclinical and clinical scanners. These achievements, coupled with interest in the molecular imaging of anatomy and physiology, and combined with a cadre of innovative agents, have brought the concept of (19)F into early clinical evaluation. In this review, we attempt to provide a slice of this rich history of research and development, with a particular focus on liquid perfluorocarbon compound-based agents.
    Preview · Article · Dec 2015
  • Dongsu Du · Shelton D. Caruthers · Carri Glide-Hurst · Daniel A. Low · H. Harold Li · Sasa Mutic · Yanle Hu
    [Show abstract] [Hide abstract] ABSTRACT: The purpose of this study was to improve triggering efficiency of the prospective respiratory amplitude-triggered 4-dimensional magnetic resonance imaging (4DMRI) method and to develop a 4DMRI imaging protocol that could offer T2 weighting for better tumor visualization, good spatial coverage and spatial resolution, and respiratory motion sampling within a reasonable amount of time for radiation therapy applications. The respiratory state splitting (RSS) and multi-shot acquisition (MSA) methods were analytically compared and validated in a simulation study by using the respiratory signals from 10 healthy human subjects. The RSS method was more effective in improving triggering efficiency. It was implemented in prospective respiratory amplitude-triggered 4DMRI. 4DMRI image datasets were acquired from 5 healthy human subjects. Liver motion was estimated using the acquired 4DMRI image datasets. The simulation study showed the RSS method was more effective for improving triggering efficiency than the MSA method. The average reductions in 4DMRI acquisition times were 36% and 10% for the RSS and MSA methods, respectively. The human subject study showed that T2-weighted 4DMRI with 10 respiratory states, 60 slices at a spatial resolution of 1.5 × 1.5 × 3.0 mm(3) could be acquired in 9 to 18 minutes, depending on the individual's breath pattern. Based on the acquired 4DMRI image datasets, the ranges of peak-to-peak liver displacements among 5 human subjects were 9.0 to 12.9 mm, 2.5 to 3.9 mm, and 0.5 to 2.3 mm in superior-inferior, anterior-posterior, and left-right directions, respectively. We demonstrated that with the RSS method, it was feasible to acquire high-quality T2-weighted 4DMRI within a reasonable amount of time for radiation therapy applications. Copyright © 2015 Elsevier Inc. All rights reserved.
    No preview · Article · Mar 2015 · International journal of radiation oncology, biology, physics
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    [Show abstract] [Hide abstract] ABSTRACT: A high r1 relaxivity manganese-gadolinium nanocolloid (αvβ3-MnOL-Gd NC) was developed and effectively detected atherosclerotic angiogenesis in rabbits fed cholesterol-rich diets for 12months using a clinical MRI scanner (3T). 3D mapping of neovasculature signal intensity revealed the spatial coherence and intensity of plaque angiogenic expansion, which may, with other high risk MR bioindicators, help identify high-risk patients with moderate (40% to 60%) vascular stenosis. Microscopy confirmed the predominant media and plaque distribution of fluorescent αvβ3-MnOL-Gd NC, mirroring the MR data. An expected close spatial association of αvβ3-integrin neovasculature and macrophages was noted, particularly within plaque shoulder regions. Manganese oleate bioelimination occurred via the biliary system into feces. Gd-DOTA was eliminated through the bile-fecal and renal excretion routes. αvβ3-MnOL-Gd NC offers an effective vehicle for T1w neovascular imaging in atherosclerosis. Copyright © 2015. Published by Elsevier Inc.
    Full-text · Article · Jan 2015 · Nanomedicine Nanotechnology Biology and Medicine
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    [Show abstract] [Hide abstract] ABSTRACT: High-relaxivity T1-weighted (T1w) MR molecular imaging nanoparticles typically present high surface gadolinium payloads that can elicit significant acute complement activation (CA). The objective of this research was to develop a high T1 contrast nanoparticle, which reduced gadolinium exposure, minimized gadolinium transmetallation risk, and elicited negligible acute complement activation. We report the development, optimization, and characterization of a gadolinium-manganese hybrid nanocolloid (MnOL-Gd NC; 138±10 (Dav)/nm; PDI: 0.06; zeta: -27±2mV). High r1 particulate relaxivity with minute additions of Gd-DOTA-lipid conjugate to the MnOL nanocolloid surface achieved an unexpected paramagnetic synergism. This hybrid MnOL-Gd NC provided optimal MR TSE signal intensity at 5nM/voxel and lower levels, consistent with the level expression anticipated for sparse biomarkers such as neovascular integrins. MnOL NC produced optimal MR TSE signal intensity at 10nM/voxel concentrations and above. Importantly, MnOL-Gd NC avoided acute CA in vitro and in vivo, while retaining minimal transmetallation risk. Copyright © 2015. Published by Elsevier Inc.
    Full-text · Article · Jan 2015 · Nanomedicine Nanotechnology Biology and Medicine
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    Matthew J. Goette · Gregory M. Lanza · Shelton D. Caruthers · Samuel A. Wickline
    [Show abstract] [Hide abstract] ABSTRACT: PurposeTo improve 19F flip angle calibration and compensate for B1 inhomogeneities in quantitative 19F MRI of sparse molecular epitopes with perfluorocarbon (PFC) nanoparticle (NP) emulsion contrast agents.Materials and Methods Flip angle sweep experiments on PFC-NP point source phantoms with three custom-designed 19F/1H dual-tuned coils revealed a difference in required power settings for 19F and 1H nuclei, which was used to calculate a calibration ratio specific for each coil. An image-based correction technique was developed using B1-field mapping on 1H to correct for 19F and 1H images in two phantom experiments.ResultsOptimized 19F peak power differed significantly from that of 1H power for each coil (P < 0.05). A ratio of 19F/1H power settings yielded a coil-specific and spatially independent calibration value (surface: 1.48 ± 0.06; semicylindrical: 1.71 ± 0.02, single-turn-solenoid: 1.92 ± 0.03). 1H-image-based B1 correction equalized the signal intensity of 19F images for two identical 19F PFC-NP samples placed in different parts of the field, which were offset significantly by ∼66% (P < 0.001), before correction.Conclusion19F flip angle calibration and B1-mapping compensations to the 19F images employing the more abundant 1H signal as a basis for correction resulted in a significant change in the quantification of sparse 19F MR signals from targeted PFC NP emulsions. J. Magn. Reson. Imaging 2014.
    Full-text · Article · Nov 2014 · Journal of Magnetic Resonance Imaging
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    [Show abstract] [Hide abstract] ABSTRACT: Restoring an antithrombotic surface to suppress ongoing thrombosis is an appealing strategy for treatment of acute cardiovascular disorders such as erosion of atherosclerotic plaque. An antithrombotic surface would present an alternative to systemic anticoagulation with attendant risks of bleeding. We have designed thrombin-targeted nanoparticles (NPs) that bind to sites of active clotting to extinguish local thrombin activity and inhibit platelet deposition while exhibiting only transient systemic anticoagulant effects. Perfluorocarbon nanoparticles (PFC NP) were functionalized with thrombin inhibitors (either D-phenylalanyl-L-prolyl-L-arginyl-chloromethyl ketone or bivalirudin) by covalent attachment of more than 15 000 inhibitors to each PFC NP. Fibrinopeptide A (FPA) ELISA demonstrated that thrombin-inhibiting NPs prevented cleavage of fibrinogen by both free and clot-bound thrombin. Magnetic resonance imaging (MRI) confirmed that a layer of thrombin-inhibiting NPs prevented growth of clots in vitro. Thrombin-inhibiting NPs were administered in vivo to C57BL6 mice subjected to laser injury of the carotid artery. NPs significantly delayed thrombotic occlusion of the artery, whereas an equivalent bolus of free inhibitor was ineffective. For thrombin-inhibiting NPs, only a short-lived (~10 min) systemic effect on bleeding time was observed, despite prolonged clot inhibition. Imaging and quantification of in vivo antithrombotic NP layers was demonstrated by MRI of the PFC NP. 19F MRI confirmed colocalization of particles with arterial thrombi, and quantitative 19F spectroscopy demonstrated specific binding and retention of thrombin-inhibiting NPs in injured arteries. The ability to rapidly form and image a new antithrombotic surface in acute vascular syndromes while minimizing risks of bleeding would permit a safer method of passivating active lesions than current systemic anticoagulant regimes.
    Full-text · Article · Sep 2014 · Nanotechnology
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    [Show abstract] [Hide abstract] ABSTRACT: Expanded and aberrant bronchial vascularity, a prominent feature of the chronic asthmatic airway, might explain persistent airway wall edema and sustained leukocyte recruitment. Since it is well established that there are causal relationships between exposure to house dust mite (HDM) and the development of asthma, determining the effects of HDM in rats, mammals with a bronchial vasculature similar to humans, provides an opportunity to study the effects of bronchial angiogenesis on airway function directly. We studied rats exposed bi-weekly to HDM (Der p 1; 50 μg/challenge by intranasal aspiration, 1, 2, 3 weeks) and measured the time course of appearance of increased blood vessels within the airway wall. Results demonstrated that within 3 weeks of HDM exposure, the number of vessels counted within airway walls of bronchial airways (0.5-3 mm perimeter) increased significantly. These vascular changes were accompanied by increased airway responsiveness to methacholine. A shorter exposure regimen (2 weeks of bi-weekly exposure) was insufficient to cause a significant increase in functional vessels or reactivity. Yet, (19)F/(1)H MR imaging at 3T following αvβ3-targeted perfluorocarbon nanoparticle infusion revealed a significant increase in (19)F signal in rat airways after 2 weeks of bi-weekly HDM, suggesting earlier activation of the process of neovascularization. Although many antigen-induced mouse models exist, mice lack a bronchial vasculature and consequently lack the requisite human parallels to study bronchial edema. Overall, our results provide an important new model to study the impact of bronchial angiogenesis on chronic inflammation and airways hyperreactivity.
    Full-text · Article · Aug 2014 · Angiogenesis
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    [Show abstract] [Hide abstract] ABSTRACT: PurposeA novel technique for highly sensitive detection of multiresonant fluorine imaging agents was designed and tested with the use of dual-frequency 19F/1H ultrashort echo times (UTE) sampled with a balanced steady-state free precession (SSFP) pulse sequence and three-dimensional (3D) radial readout.Methods Feasibility of 3D radial balanced UTE-SSFP imaging was demonstrated for a phantom comprising liquid perfluorooctyl bromide (PFOB). Sensitivity of the pulse sequence was measured and compared with other sequences imaging the PFOB (CF2)6 line group including UTE radial gradient-echo (GRE) at α = 30°, as well as Cartesian GRE, balanced SSFP, and fast spin-echo (FSE). The PFOB CF3 peak was also sampled with FSE.ResultsThe proposed balanced UTE-SSFP technique exhibited a relative detection sensitivity of 51 min−1/2 (α = 30°), at least twice that of other sequence types with either 3D radial (UTE GRE: 20 min−1/2) or Cartesian k-space filling (GRE: 12 min−1/2; FSE: 16 min−1/2; balanced SSFP: 23 min−1/2). In vivo imaging of angiogenesis-targeted PFOB nanoparticles was demonstrated in a rabbit model of cancer on a clinical 3 Tesla scanner.ConclusionA new dual 19F/1H balanced UTE-SSFP sequence manifests high SNR, with detection sensitivity more than two-fold better than traditional techniques, and alleviates imaging problems caused by dephasing in complex spectra. Magn Reson Med 000:000–000, 2014. © 2014 Wiley Periodicals, Inc.
    Full-text · Article · Aug 2014 · Magnetic Resonance in Medicine
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    Erina Ghosh · Shelton D Caruthers · Sandor J. Kovacs
    [Show abstract] [Hide abstract] ABSTRACT: The Doppler echocardiographic E-wave is generated when the left ventricle's suction pump attribute initiates transmitral flow. In some subjects E-waves are accompanied by L-waves whose occurrence has been correlated with diastolic dysfunction. The mechanisms for L-wave generation have not been fully elucidated. We propose that the recirculating diastolic intraventricular vortex ring generates L-waves and based on this mechanism, we predict the presence of L-waves in the right ventricle (RV). We imaged intraventricular flow using Doppler echocardiography and phase-contrast magnetic resonance imaging (PC-MRI) in ten healthy volunteers. L-waves were recorded in all subjects with highest velocities measured typically 2 cm below the annulus. Fifty-five percent of cardiac cycles (189 of 345) had L-waves. Color M-mode images eliminated mid-diastolic transmitral flow as the cause of the observed L-waves. 3-D intraventricular flow patterns were imaged via PC-MRI and independently validated our hypothesis. Additionally as predicted, L-waves were observed in the RV, by both echocardiography and PC-MRI. The re-entry of the E-wave generated vortex ring flow through a suitably located echo sample volume can be imaged as the L-wave. These waves are a general feature and a direct consequence of LV and RV diastolic fluid mechanics.
    Full-text · Article · Jun 2014 · Journal of Applied Physiology
  • [Show abstract] [Hide abstract] ABSTRACT: We sought to develop a unique sensor-reporter approach for functional kidney imaging that employs circulating perfluorocarbon nanoparticles and multinuclear (1) H/(19) F MRI. (19) F spin density weighted and T1 weighted images were used to generate quantitative functional mappings of both healthy and ischemia-reperfusion (acute kidney injury) injured mouse kidneys. (1) H blood-oxygenation-level-dependent (BOLD) MRI was also employed as a supplementary approach to facilitate the comprehensive analysis of renal circulation and its pathological changes in acute kidney injury. Heterogeneous blood volume distributions and intrarenal oxygenation gradients were confirmed in healthy kidneys by (19) F MRI. In a mouse model of acute kidney injury, (19) F MRI, in conjunction with blood-oxygenation-level-dependent MRI, sensitively delineated renal vascular damage and recovery. In the cortico-medullary junction region, we observed 25% lower (19) F signal (P < 0.05) and 70% longer (1) H T2* (P < 0.01) in injured kidneys compared with contralateral kidneys at 24 h after initial ischemia-reperfusion injury. We also detected 71% higher (19) F signal (P < 0.01) and 40% lower (1) H T2* (P < 0.05) in the renal medulla region of injured kidneys compared with contralateral uninjured kidneys. Integrated (1) H/(19) F MRI using perfluorocarbon nanoparticles provides a multiparametric readout of regional perfusion defects in acutely injured kidneys. Magn Reson Med, 2013. © 2013 Wiley Periodicals, Inc.
    No preview · Article · Jun 2014 · Magnetic Resonance in Medicine
  • D Du · S Caruthers · C Glide-Hurst · D Low · S Mutic · Y Hu
    [Show abstract] [Hide abstract] ABSTRACT: Purpose: To develop an imaging technique that enables us to acquire T2- weighted 4D Magnetic Resonance Imaging (4DMRI) with sufficient spatial coverage, temporal resolution and spatial resolution for clinical evaluation.
    No preview · Article · Jun 2014 · Medical Physics
  • [Show abstract] [Hide abstract] ABSTRACT: Due to their small size, lower cost, short reproduction cycle, and genetic manipulation, rodents have been widely used to test the safety and efficacy for pharmaceutical development in human disease. In this report, MRI cholangiography demonstrated an unexpected rapid (<5min) biliary elimination of gadolinium-perfluorocarbon nanoparticles (approximately 250nm diameter) into the common bile duct and small intestine of rats, which is notably different from nanoparticle clearance patterns in larger animals and humans. Unawareness of this dissimilarity in nanoparticle clearance mechanisms between small animals and humans may lead to fundamental errors in predicting nanoparticle efficacy, pharmacokinetics, biodistribution, bioelimination, and toxicity.
    No preview · Article · May 2014 · Nanomedicine: nanotechnology, biology, and medicine
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    [Show abstract] [Hide abstract] ABSTRACT: Bicuspid pulmonary valves and pulmonary artery aneurysms are two rare entities, reported in association, and usually attributed to hemodynamic alterations caused by the bicuspid pulmonary valve. We present magnetic resonance images of a patient with a bicuspid pulmonary valve and pulmonary artery aneurysm, and propose an alternative mechanism for this association, based on recent embryologic studies that link anomalies of the semilunar valves and great vessels with derangement of the cardiac neural crest cell development.
    Preview · Article · Apr 2014
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    [Show abstract] [Hide abstract] ABSTRACT: In nanomedicine, the hydrophobic nature of paclitaxel has favored its incorporation into many nanoparticle formulations for anti-cancer chemotherapy. At lower doses taxanes are reported to elicit anti-angiogenic responses. In the present study, the facile synthesis, development and characterization of a new lipase-labile docetaxel prodrug is reported and shown to be an effective anti-angiogenic agent in vitro and in vivo. The Sn 2 phosphatidylcholine prodrug was stably incorporated into the lipid membrane of αvβ3-integrin targeted perfluorocarbon (PFC) nanoparticles (αvβ3-Dxtl-PD NP) and did not appreciably release during dissolution against PBS buffer or plasma over three days. Overnight exposure of αvβ3-Dxtl-PD NP to plasma spiked with phospholipase enzyme failed to liberate the taxane from the membrane until the nanoparticle integrity was compromised with alcohol. The bioactivity and efficacy of αvβ3-Dxtl-PD NP in endothelial cell culture was as effective as Taxol(®) or free docetaxel in methanol at equimolar doses over 96 hours. The anti-angiogenesis effectiveness of αvβ3-Dxtl-PD NP was demonstrated in the Vx2 rabbit model using MR imaging of angiogenesis with the same αvβ3-PFC nanoparticle platform. Nontargeted Dxtl-PD NP had a similar MR anti-angiogenesis response as the integrin-targeted agent, but microscopically measured decreases in tumor cell proliferation and increased apoptosis were detected only for the targeted drug. Equivalent dosages of Abraxane(®) given over the same treatment schedule had no effect on angiogenesis when compared to control rabbits receiving saline only. These data demonstrate that αvβ3-Dxtl-PD NP can reduce MR detectable angiogenesis and slow tumor progression in the Vx2 model, whereas equivalent systemic treatment with free taxane had no benefit.
    Full-text · Article · Mar 2014 · Theranostics
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    [Show abstract] [Hide abstract] ABSTRACT: MR cholangiography shows unexpected, rapid excretion of 250 nm-sized paramagnetic perfluorocarbon nanoparticles into the rat bile duct and small intestine in less than 5 minutes.
    Full-text · Article · Jan 2014
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    No preview · Dataset · Jan 2014
  • [Show abstract] [Hide abstract] ABSTRACT: The development of perfluorocarbon (PFC) nanoparticles has been an incremental but expanding plan of technology development intended to bring a family of product options to patients with intractable diseases. PFC nanoparticles are a multifunctional platform technology with versatile imaging and drug delivery potential demonstrated in a variety of preclinical animal models. The concept of targeted drug delivery to improve the safety and efficacy of pharmaceuticals by optimizing therapeutic release at the site of disease is not a new concept. The term theranostic is now commonly used to describe a nanotechnology platform designed for diagnostic molecular imaging in combination with specific delivery and release of drug into the targeted microanatomical sites. The antiangiogenic effectiveness of TNP-470, a water-soluble functional analogue of fumagillin, was widely demonstrated in rodents and later studied in human clinical trials.
    No preview · Chapter · Sep 2013
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    [Show abstract] [Hide abstract] ABSTRACT: Angiogenesis is an important constituent of many inflammatory pulmonary diseases, which has been unappreciated until recently. Early neovascular expansion in the lungs in preclinical models and patients is very difficult to assess noninvasively, particularly quantitatively. The present study demonstrated that (19)F/(1)H MR molecular imaging with αvβ3-targeted perfluorocarbon nanoparticles can be used to directly measure neovascularity in a rat left pulmonary artery ligation (LPAL) model, which was employed to create pulmonary ischemia and induce angiogenesis. In rats 3 days after LPAL, simultaneous (19)F/(1)H MR imaging at 3T revealed a marked (19)F signal in animals 2 h following αvβ3-targeted perfluorocarbon nanoparticles [(19)F signal (normalized to background) = 0.80 ± 0.2] that was greater (p = 0.007) than the non-targeted (0.30 ± 0.04) and the sham-operated (0.07 ± 0.09) control groups. Almost no (19)F signal was found in control right lung with any treatment. Competitive blockade of the integrin-targeted particles greatly decreased the (19)F signal (p = 0.002) and was equivalent to the non-targeted control group. Fluorescent and light microscopy illustrated heavy decorating of vessel walls in and around large bronchi and large pulmonary vessels. Focal segmental regions of neovessel expansion were also noted in the lung periphery. Our results demonstrate that (19)F/(1)H MR molecular imaging with αvβ3-targeted perfluorocarbon nanoparticles provides a means to assess the extent of systemic neovascularization in the lung.
    Full-text · Article · Aug 2013 · Angiogenesis
  • [Show abstract] [Hide abstract] ABSTRACT: We present a novel blood flow-enhanced-saturation-recovery (BESR) sequence, which allows rapid in vivo T(1) measurement of blood for both (1) H and (19) F nuclei. BESR sequence is achieved by combining homogeneous spin preparation and time-of-flight image acquisition and therefore preserves high time efficiency and signal-to-noise ratio for (19) F imaging of circulating perfluorocarbon nanoparticles comprising a perfluoro-15-crown-5-ether core and a lipid monolayer (nominal size = 250 nm). The consistency and accuracy of the BESR sequence for measuring T(1) of blood was validated experimentally. With a confirmed linear response feature of (19) F R(1) with oxygen tension in both salt solution and blood sample, we demonstrated the feasibility of the BESR sequence to quantitatively determine the oxygen tension within mouse left and right ventricles under both normoxia and hyperoxia conditions. Thus, (19) F BESR MRI of circulating perfluorocarbon nanoparticles represents a new approach to noninvasively evaluate intravascular oxygen tension. Magn Reson Med, 2012. © 2012 Wiley Periodicals, Inc.
    No preview · Article · Jul 2013 · Magnetic Resonance in Medicine
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    [Show abstract] [Hide abstract] ABSTRACT: Purpose: To assess the dependence of neovascular molecular magnetic resonance (MR) imaging on relaxivity (r1) of αvβ3-targeted paramagnetic perfluorocarbon (PFC) nanoparticles and to delineate the temporal-spatial consistency of angiogenesis assessments for individual animals. Materials and methods: Animal protocols were approved by the Washington University Animal Studies Committee. Proton longitudinal and transverse relaxation rates of αvβ3-targeted and nontargeted PFC nanoparticles incorporating gadolinium diethylenetrianime pentaacedic acid (Gd-DTPA) bisoleate (BOA) or gadolinium tetraazacyclododecane tetraacetic acid (Gd-DOTA) phosphatidylethanolamine (PE) into the surfactant were measured at 3.0 T. These paramagnetic nanoparticles were compared in 30 New Zealand White rabbits (four to six rabbits per group) 14 days after implantation of a Vx2 tumor. Subsequently, serial MR (3.0 T) neovascular maps were developed 8, 14, and 16 days after tumor implantation by using αvβ3-targeted Gd-DOTA-PE nanoparticles (n = 4) or nontargeted Gd-DOTA-PE nanoparticles (n = 4). Data were analyzed with analysis of variance and nonparametric statistics. Results: At 3.0 T, Gd-DTPA-BOA nanoparticles had an ionic r1 of 10.3 L · mmol(-1) · sec(-1) and a particulate r1 of 927000 L · mmol(-1) · sec(-1). Gd-DOTA-PE nanoparticles had an ionic r1 of 13.3 L · mmol(-1) · sec(-1) and a particulate r1 of 1 197000 L · mmol(-1) · sec(-1). Neovascular contrast enhancement in Vx2 tumors (at 14 days) was 5.4% ± 1.06 of the surface volume with αvβ3-targeted Gd-DOTA-PE nanoparticles and 3.0% ± 0.3 with αvβ3-targeted Gd-DTPA-BOA nanoparticles (P = .03). MR neovascular contrast maps of tumors 8, 14, and 16 days after implantation revealed temporally consistent and progressive surface enhancement (1.0% ± 0.3, 4.5% ± 0.9, and 9.3% ± 1.4, respectively; P = .0008), with similar time-dependent changes observed among individual animals. Conclusion: Temporal-spatial patterns of angiogenesis for individual animals were followed to monitor longitudinal tumor progression. Neovasculature enhancement was dependent on the relaxivity of the targeted agent.
    Full-text · Article · Jun 2013 · Radiology