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Biomedical subjects

A Bjørnerud

Publications and source records attributed to A Bjørnerud.

15 recordsLinked to original sources

Contrast-enhanced dynamic magnetic resonance imaging of finger joints in osteoarthritis and rheumatoid arthritis: an analysis based on pharmacokinetic modeling.

PURPOSE: To investigate a two-compartment kinetic model applied to the dynamic time course of contrast enhancement as a method to differentiate between finger-joint synovitis in established osteoarthritis (OA) and rheumatoid arthritis (RA). MATERIAL AND METHODS: Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) of one hand in 19 patients and six healthy volunteers was undertaken. Eight patients had OA of the hand and eleven patients had RA. From the signal intensity curves, the three parameters Kps (endothelial transfer constant), Kep (elimination rate constant from extracellular space back to plasma) and Kel (elimination rate constant from plasma by renal excretion) were calculated. RESULTS: The rate constant Kps showed the best separation between the groups with significantly higher values in the RA group compared to the OA group (P<0.005) and in the OA group compared to the control group (P<0.005). Significantly higher values of Kep were also found in the RA group compared with the OA group (P<0.005). CONCLUSION: DCE-MRI may provide useful information that can help differentiate synovitis in OA from synovitis in RA.

Arthritis, Rheumatoid↗

A targeted contrast agent for magnetic resonance imaging of thrombus: implications of spatial resolution.

A preparation of ultra-small superparamagnetic iron oxide (USPIO) particles coupled to an RGD peptide (RGD-USPIO) was investigated as an MR contrast agent, targeted to activated platelets, in both ex vivo and in vivo thrombus models. Thrombus visualization ex vivo was compared using RGD-USPIO and a non-targeted UPSIO. The influence of thrombus visualization on thrombus exposure time to RGD-USPIO (ex vivo) and on the spatial resolution of the MR image (ex vivo and in vivo) was assessed. RGD-USPIO resulted in better thrombus visualization than non-targeted USPIO ex vivo, and maximum enhancement was achieved after approximately one hour exposure time of the thrombus to RGD-USPIO. The ability to visualize the clots was highly dependent on the spatial resolution of the image. In vivo, an in-plane resolution of less than 0.2 x 0.2 mm(2) was required for good clot visualization after contrast enhancement. It is concluded that the achievable resolution and sensitivity is a potential limitation to the usefulness of active vascular targeting in MRI.

Animals↗

Pre-clinical results with Clariscan (NC100150 Injection); experience from different disease models.

A superparamagnetic nanoparticle (NC100150 Injection) was investigated in two different animal models; renal perfusion in pigs and tumour imaging in mice. In the pig model, qualitative first-pass perfusion maps following a bolus injection of NC100150 Injection enabled good visualisation of hypoperfused regions of the renal cortex following partial ligation of the renal artery. High temporal resolution was found to be essential to accurately capture the first passage of the contrast agent through the kidney due to the very rapid blood flow in normal renal cortex. In the tumour model (LS174T cells implanted in nude mice), NC100150 Injection was found to cause a gradual (over 60 min) signal increase on T1-w images in part of the tumours which was attributed to contrast agent leakage from the vascular space to the extravascular space in areas of increased capillary permeability. This observation is consistent with previous reports on the molecular cut-off size for vascular extraction for this tumour cell line. The specific enhancement of tumour tissue suggest potential utility of NC100150 Injection as an angiogenesis marker.

Adenocarcinoma↗

pH-sensitive paramagnetic liposomes as MRI contrast agents: in vitro feasibility studies.

A novel type of pH-sensitive paramagnetic contrast agent is introduced; a low molecular weight gadolinium (Gd) chelate (GdDTPA-BMA) encapsulated within pH-sensitive liposomes. The in vitro relaxometric properties of the liposomal Gd chelate were shown to be a function of the pH in the liposomal dispersion and the membrane composition. Only a minor pH-dependency of the T1 relaxivity (r1) was observed for liposomal GdDTPA-BMA composed of the unsaturated lipids dioleoyl phosphatidyl ethanolamine (DOPE) and oleic acid (OA). On the other hand, the r1 of GdDTPA-BMA encapsulated within saturated dipalmitoyl phosphatidyl ethanolamine/palmitic acid (DPPE/PA) liposomes demonstrated a strong pH-dependency. At physiological pH and above, the r1 of this system was significantly lowered compared to that of non-liposomal Gd chelate, which was explained by an exchange limited relaxation process. Lowering the pH below physiological value, however, gave a sharp and 6-7 fold increase in r1, due to liposome destabilisation and subsequent leakage of entrapped GdDTPA-BMA. The pH-sensitivity of the DPPE/PA liposome system was confirmed in an in vitro magnetic resonance imaging (MRI) phantom study.

Contrast Media↗

NC100150 Injection, a preparation of optimized iron oxide nanoparticles for positive-contrast MR angiography.

A preparation of monocrystalline iron oxide nanoparticles with an oxidized starch coating, currently in clinical trials (NC100150 Injection; CLARISCAN), was characterized by magnetization measurements, relaxometry, and photon correlation spectroscopy. By combining the results with a measure of iron content, one can obtain the size and magnetic attributes of the iron cores, including the relevant correlation times for outer sphere relaxation (tau(SO) and tau(D)), and information about the interaction of the organic coating with both core and solvent. The results are 6.43 nm for the iron oxide core diameter, a magnetic moment of 4.38x10(-17) erg/G, and a water-penetrable coating region of oxidized oligomeric starch fragments and entrained water molecules. The latter extends the hydrodynamic diameter to 11.9 nm and lowers the average diffusivity of solvent about 64% (which increases tau(D) accordingly). The nanoparticles show little size-polydispersity, evidenced by the lowest value of r(2)/r(1) at 20 MHz reported to date, an asset for magnetic resonance angiography.

Contrast Media↗

Effect of NC100150 injection on the (1)H NMR linewidth of human whole blood ex vivo: dependency on blood oxygen tension.

The linewidth of the (1)H NMR signal (7.05 T) of human whole blood titrated with a superparamagnetic contrast agent (NC100150 injection) was evaluated at different blood oxygen tensions. In deoxygenated blood and low contrast agent concentrations, NC100150 injection caused a decrease in linewidth. After reaching a minimum, the linewidth increased as the concentration of NC100150 injection increased. At the concentration corresponding to the minimum linewidth, the magnetization of the extracellular space containing the NC100150 injection was equal to that of the paramagnetic (deoxygenated hemoglobin) intracellular space. The minimum linewidth is therefore consistent with a complete elimination of the local microscopic susceptibility effect, the major cause of linebroadening. Additionally, phantom studies were performed at 1.5 T, confirming that the contrast enhancement of NC100150 injection in blood is dependent on oxygen tension. The data suggest that NC100150 injection may be useful in differentiating vessels with varying relative oxygen tensions.

Blood↗

Thermosensitive paramagnetic liposomes for temperature control during MR imaging-guided hyperthermia: in vitro feasibility studies.

RATIONALE AND OBJECTIVES: Magnetic resonance (MR) imaging-based temperature monitoring has gained interest for use in general hyperthermia treatment of tumors. Such therapy requires an accurate control of the temperature, which should range from 41 degrees to 45 degrees C. A novel type of thermosensitive MR agent is proposed: liposome-encapsulated gadolinium chelates whose temperature response is linked to the phase-transition properties of the liposome carrier. In vitro relaxometry and MR imaging were used to evaluate the thermosensitivity of the contrast properties of liposomal gadolinium diethylenetriaminepentaacetic acid bis(methylamide) (Gd-DTPA-BMA). MATERIALS AND METHODS: T1 relaxivity (rl) measurements of liposomal Gd-DTPA-BMA were undertaken at 0.47 T and at temperatures of 20 degrees-48 degrees C. MR imaging was performed at 2.0 T with a gel phantom containing inserts of liposomes. Diffusion-weighted and T1-weighted gradient-recalled echo images were acquired as the phantom was heated from 22 degrees to about 65 degrees C. RESULTS: At ambient temperature, the r1 of liposomal Gd-DTPA-BMA was exchange limited due to slow water exchange between the liposome interior and exterior. A sharp, marked increase in r1 occurred as the temperature reached and exceeded the gel-to-liquid crystalline phase-transition temperature (Tm) of the liposomes (42 degrees C). The relaxation enhancement was mainly attributable to the marked increase in transmembrane water permeability, yielding fast exchange conditions. There was good correlation between the relaxometric and imaging results; the signal intensity on T1-weighted gradient-recalled echo images increased markedly as the temperature approached Tm. The temperature sensitivity of the diffusion-weighted technique differed from that of the liposome-based T1-weighted approach, with an apparent water diffusion coefficient increasing linearly with temperature. CONCLUSION: Since the transition from low to high signal intensity occurred in the temperature range of 38 degrees - 42 degrees C, the investigated paramagnetic liposomes have a potential role as "off-on" switches for temperature control during hyperthermia treatment.

Contrast Media↗

CBF and CBV measurements by USPIO bolus tracking: reproducibility and comparison with Gd-based values.

The authors measured cerebral blood flow (CBF) and cerebral blood volume (CBV) by bolus tracking of a novel ultrasmall superparamagnetic iron oxide (USPIO) contrast agent (NC100150) and compared absolute and relative perfusion measurements with those obtained by a standard gadolinium-based contrast agent. They found a linear correlation between the two methods. A dose of 0.4 mg Fe/kg body weight was found to produce a signal drop similar to that of a standard 0.2 mmol/kg gadodiamide injection using spin-echo echoplanar imaging (SE-EPI) at 1.0 T. The measurements showed a high degree of reproducibility of repeated absolute as well as relative CBF and CBV values, lending further hope to the possibility of using magnetic resonance bolus tracking for routine CBF and CBV measurements. Finally, the authors present their initial experience with high-resolution, non-EPI CBV maps obtained from steady-state levels of an intravascular superparamagnetic contrast agent.

Animals↗

NC100150-enhanced 3D-SPGR MR angiography of the common carotid artery in a pig vascular stenosis model. Quantification of stenosis and dose optimization.

PURPOSE: NC100150 is a new type of ultra-small iron oxide (USPIO) blood pool agent. The aim of this study was to compare NC100150-enhanced MR angiography (MRA) to time-of-flight (TOF) MRA, phase-contrast (PC) MRA, and digital subtraction angiography (DSA) in experimental stenoses in pigs, and furthermore to determine the optimal dose of the contrast agent. MATERIAL AND METHODS: An experimental stenosis of the right and left common carotid artery (CCA) was applied surgically in 6 Yorkshire pigs. DSA was performed as the gold standard, followed by 3D-TOF, 3D-PC, and NC100150-enhanced MRA. RESULTS: Eleven stenoses of the CCA were successfully applied. The degree of the stenosis, determined by NC100150-enhanced MRA, did not differ significantly from DSA, whereas TOF and PC MRA underestimated it. The image quality of the NC100150-enhanced MRA was superior to both TOF and PC MRA. The optimal dose of NC100150 was 5-6 mg Fe/kg, since higher doses did not further increase signal-to-noise ratio or contrast-to-noise ratio. There was a linear relationship between blood relaxation rate and contrast dose. CONCLUSION: NC100150-enhanced MRA has the potential for quantification of carotid stenoses and provides an alternative to DSA. The optimal dose of NC100150 was 5-6 mg Fe/kg.

Angiography, Digital Subtraction↗

[Experimental evaluation of superparamagnetic iron oxide particles in pulmonary MR angiography].

PURPOSE: Initial experimental results of contrast-enhanced pulmonary MR angiography using the new superparamagnetic iron oxide blood pool agent FeO-BPA. METHOD: Pulmonary MRA was performed in 7 domestic pigs using a cardiac-triggered coronal T1-weighted FFE-Sequence before and up to 90 minutes after contrast injection obtained on a 1.5 T magnet with a standard gradient equipment. A dose of 4 mg Fe/kg bodyweight was used for MRA. The images were qualitatively assessed and compared with X-ray i.v.-DSA. RESULTS: The injection of FeO-BPA allows the acquisition of unsaturated in-plane images of the pulmonary vascular tree down to the first order subsegmental branches including vessel diameters of approximately 1.5 mm. In the normal non-occluded vasculature, no signal void is seen in the TE range of 2.8-5.5 ms secondary to exceeding susceptibility effects which are caused by the iron oxide accumulation. Even 90 minutes after injection of FeO-BPA, assessment of the pulmonary vasculature is still satisfactory. CONCLUSIONS: In the animal experiment, the use of the blood pool agent FeO-BPA provides detailed pulmonary angiograms even on a magnet with a conventional gradient system. The major advantage is the comfortable diagnostic window of > 1.5 hours which also portends its utility for future MR-guided pulmonary interventions.

Angiography, Digital Subtraction↗

Abdominal MR angiography performed using blood pool contrast agents: comparison of a new superparamagnetic iron oxide nanoparticle and a linear gadolinium polymer.

OBJECTIVE: We evaluated and compared two different experimental blood pool contrast agents for abdominal MR angiography in an animal model. MATERIALS AND METHODS: In seven pigs, coronal T1-weighted three-dimensional fast field-echo images were obtained on a conventional 1.5-T MR imaging system before and after i.v. injection of the ultrasmall superparamagnetic iron oxide agent FeO-BPA. In another seven pigs, MR angiograms were acquired using the gadolinium polymer WIN 22181. Enhanced images were obtained 5-210 min after injection of FeO-BPA and 1-120 min after injection of WIN 22181. RESULTS: Both blood pool agents yielded detailed angiograms of the abdominal vascular tree when imaging lasted 2 min. In-plane running vessels were imaged without saturation effects and with equivalent maximum signal-to-noise ratios. Half the maximum signal-to-noise ratio was reached 150 min after injection of FeO-BPA, whereas this interval was approximately 70 min for the gadolinium polymer. Because of these different imaging half-life periods, the effective diagnostic window provided by FeO-BPA was six to eight times longer than that of WIN 22181. In the liver, the vascular T1 shortening and the parenchymal T2* effect of FeO-BPA complemented each other, resulting in an optimal contrast-to-noise ratio significantly higher than that achieved with WIN 22181. This "double-contrast effect" in the liver was especially helpful when obtaining detailed MR portograms. CONCLUSION: The blood pool agents FeO-BPA and WIN 22181 can be used to produce high-quality abdominal MR angiograms on standard MR imaging equipment. The contrast-to-noise ratio of hepatic vessels is best on iron oxide-enhanced images because of a T1-T2* synergistic effect in the liver. The longer diagnostic window provided by FeO-BPA coupled with the option of in-plane imaging suggests the usefulness of FeO-BPA in future MR imaging-guided vascular interventions.

Abdomen↗

NMR relaxation studies with MnDPDP.

PURPOSE: Our studies were designed to compare the efficacy of mangafodipir trisodium (MnDPDP, Teslascan) as a tissue-specific MR agent with that of manganese chloride (MnCl2), to compare the efficacy of different doses and rates of administration of MnDPDP, and to collect the data needed for predicting optimum pulse sequences. MATERIAL AND METHODS: The dose response for the relaxation rates R1 and R2 at 0.47 T, and the manganese (Mn) concentrations in rat liver and in the liver, pancreas, heart and adrenals of pigs was determined for both MnDPDP and MnCl2 administered i.v. Computer simulations were carried out to model the effects of different tissue Mn concentrations and TR on signal intensities and contrast-to-noise ratios. RESULTS: In rat liver and pig organs both compounds produced a positive dose-response in R1 and tissue Mn concentration, and only small or no response in R2. The Mn concentration in rat liver was positively correlated with R1, regardless of the form in which Mn was given, or the rate of administration. Optimal imaging parameters are therefore expected to be different pre- and post-MnDPDP administration. CONCLUSION: The added cardiovascular safety of MnDPDP compared with MnCl2 does not result in loss of efficacy in increasing RI at the intended clinical dose of 5 mumol/kg MnDPDP. The changes in R2 were too small to affect T2-weighted images. The data give the basis for choosing the appropriate pulse sequences for MnDPDP-enhanced MR imaging.

Animals↗

Contrast-enhanced magnetic resonance urography. First experimental results with a polymeric gadolinium bloodpool agent.

RATIONALE AND OBJECTIVES: The authors investigated the feasibility of contrast-enhanced excretory magnetic resonance urography to visualize the nonobstructed urinary tract with a macromolecular gadolinium-based bloodpool agent. METHODS: Excretory magnetic resonance imaging was performed in seven pigs using a T1-weighted three dimensional fast-field-echo sequence before and up to 120 minutes after administration of a gadolinium bloodpool prototype agent. RESULTS: During the first 15 minutes after injection, the urographic effect was predominantly poor. Visualization of the entire urinary tract was excellent in four pigs and incomplete but satisfactory in three 105 minutes after injection. Furosemide application was tested in one case, which improved image quality effectively. Corresponding to the physiological excretion rate, signal measurements in the renal parenchyma revealed a gradual decrease of the initially distinct contrast enhancement. CONCLUSIONS: T1-weighted contrast-enhanced magnetic resonance urography using a polymeric gadolinium bloodpool allows detailed visualization of the normal urinary tract, while information about the excretory function is obtained simultaneously. However, application of a diuretic seems to be essential to prevent lengthy examination duration.

Animals↗