Contrast-enhanced 3D-TOF MRA of peripheral vessels: intravascular versus extracellular MR contrast media.

MR contrast media have been used to improve MR angiography (MRA). Their effect has been particularly beneficial for extracranial MRA. This study evaluated the efficacy of a new formulation of ultrasmall superparamagnetic iron oxide particles (USPIO) on three-dimensional (3D) time of flight (TOF) MRA in the pelvis and lower limb circulation. Each of six dogs received 3 mg/kg of USPIO and .2 mmol/kg of gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA) bis-methylamide (BMA) by intravenous infusion on separate examinations. Precontrast and postcontrast 3D-TOF MRA images of the lower extremities were acquired over the course of 45 minutes postinjection. Signal intensity (SI) was measured on axial views along the external iliac, femoral, and popliteal arteries. USPIO provided clear demarcation of the major primary, secondary, and tertiary vessels and the improved contrast-to-noise ratio (CNR) was maintained for 45 minutes. Gd-DTPA-BMA provided less signal enhancement than USPIO. The increase in CNR with this agent had significantly declined by 15 minutes after injection. The major vessels could no longer be visualized at 30 and 45 minutes after injection of Gd-DTPA-BMA This study demonstrates the efficacy of USPIO as a contrast medium for 3D-TOF MRA. It was concluded that USPIO provided effective and persistent enhancement of the peripheral vessels.

A study of the contribution of changes in the cerebral blood volume to the haemodynamic response to anoxia in rat brain.

A susceptibility contrast agent which does not pass into the extra-cellular space was used to study the effect of changes in the relative cerebral blood volume (CBV) on the haemodynamic response to anoxia, for both normal and ischaemic brain tissue, in a rat model of acute focal ischaemia. In non-ischaemic tissue a strong CBV component was observed in the haemodynamic response, both during and after anoxia. During anoxia the change in the CBV of the non-ischaemic tissue was estimated to be 40% in the caudate putamen and 70% in the frontal-parietal cortex. For severely ischaemic tissue (ischaemic caudate putamen) there was no change in the CBV during anoxia while in areas of moderate ischaemia (ischaemic frontal parietal cortex) a change of 20% was observed. The effect of the contrast agent on spin-echo images was consistent with a small reduction in the microvascular blood volume of the ischaemic tissue.

Comparison of dysprosium DTPA BMA and superparamagnetic iron oxide particles as susceptibility contrast agents for perfusion imaging of regional cerebral ischemia in the rat.

The aim of the study was to compare the first-passage profiles of dysprosium diethylenetriamine penta-acetic acid bis(methylamide) (DTPA BMA) and the superparamagnetic iron oxide particles NSR 0430 in regions with severe and moderate cerebral ischemia. In seven rats subjected to middle cerebral artery occlusion, two dynamic MR perfusion imaging series were acquired after intravenous bolus injections of .5 mmol/kg dysprosium DTPA BMA and .06 mmolFe/kg iron oxide particles, respectively. The doses were chosen to obtain similar maximum signal change in normally perfused brain. The first-passage profiles were compared in a region of interest (ROI) in the core area with severe ischemia and in a ROI in the penumbra area of moderate ischemia. The results were compared both as the calculated mean signal intensity versus time curves for all seven rats and statistically for an estimated mean transit time (MTT) after gamma variate fitting of the calculated concentration versus time curves. The first-passage profiles for the two contrast agents were similar, both in the core area of severe ischemia and in the penumbra area of moderate ischemia. In this rat stroke model, dysprosium DTPA BMA and the superparamagnetic iron oxide particles NSR 0430 were found to be equally efficacious for the diagnosis of the perfusion deficit, but if safe for human investigations, iron oxide particles would have an advantage as equal susceptibility effect may be achieved with smaller injection volumes.

A study of the contribution of changes in the cerebral blood volume to the haemodynamic response to anoxia in rat brain.

A susceptibility contrast agent which does not pass into the extra-cellular space was used to study the effect of changes in the relative cerebral blood volume (CBV) on the haemodynamic response to anoxia, for both normal and ischaemic brain tissue, in a rat model of acute focal ischaemia. In non-ischaemic tissue a strong CBV component was observed in the haemodynamic response, both during and after anoxia. During anoxia the change in the CBV of the non-ischaemic tissue was estimated to be 40% in the caudate putamen and 70% in the frontal-parietal cortex. For severely ischaemic tissue (ischaemic caudate putamen) there was no change in the CBV during anoxia while in areas of moderate ischaemia (ischaemic frontal parietal cortex) a change of 20% was observed. The effect of the contrast agent on spin-echo images was consistent with a small reduction in the microvascular blood volume of the ischaemic tissue.

Cerebrovascular changes in rats during ischemia and reperfusion: a comparison of BOLD and first pass bolus tracking techniques.

Both first pass bolus tracking of a susceptibility contrast agent and blood oxygenation level dependent (BOLD) sequences provide information on the tissue perfusion and the cerebral blood volume, but each sequence has its own particular limitations. In this article, both techniques were used to assess the cerebrovascular changes occurring in a rat model of focal cerebral ischemia with reperfusion after 2 h of ischemia. The blood oxygenation level dependent studies were performed before, during, and after 60 s of anoxia to observe the response of the tissue to a respiratory challenge. Both techniques were able to detect ischemia and reperfusion; however, first pass bolus tracking provided better sensitivity and was easier to interpret. Because the blood oxygenation level dependent sequence did not provide any additional information, bolus tracking would appear to be the method of choice for studies of cerebral ischemia with reperfusion.

Perfusion and diffusion-weighted MR imaging for in vivo evaluation of treatment with U74389G in a rat stroke model.

BACKGROUND AND PURPOSE: The present study was performed to examine the potential of diffusion-weighted (DW) imaging and dynamic first-passage bolus tracking of susceptibility contrast agents (perfusion imaging) for early in vivo evaluation of the effects of treatment with the free radical scavenger U74389G in a rat model of temporary focal ischemia. METHODS: After 45 minutes of middle cerebral artery occlusion, the treatment group (n = 9) received an infusion of U74389G, and the control group (n = 9) received the identical volume of the vehicle. Reperfusion was instituted in both groups after 120 minutes of middle cerebral artery occlusion. The DW images were collected during middle cerebral artery occlusion and reperfusion and were compared with histologically assessed areas of tissue injury after 2 hours of reperfusion. The dynamic perfusion series were processed on a pixel-to-pixel basis to produce parametric maps reflecting the maximum reduction in the signal obtained during the first passage of the contrast agent and the time delay between the arrival of the bolus and the point of maximum contrast-agent effect. RESULTS: The area of ischemic injury, as assessed from the DW imaging at 60 minutes of reperfusion, was significantly smaller in the treatment group: 9 +/- 8% of ipsilateral hemisphere compared with 19 +/- 8% in the control group. The histological examination after 2 hours of reperfusion demonstrated an area of ischemic injury of 10 +/- 8% for the treatment group compared to 25 +/- 10% in the control group. In the treatment group, the perfusion imaging showed a reduction in time delay to maximum effect of the contrast agent in the ischemic hemisphere compared with the control group. CONCLUSIONS: The DW imaging during early reperfusion showed a protective effect of postocclusion treatment with the free radical scavenger U74389G. The improvement of time delay to maximum effect of the contrast agent observed in the perfusion imaging of the treatment group may reflect an improvement in the collateral flow to the ischemic tissue.

Dy-DTPA-BMA as an indicator of tissue viability in MR imaging. An experimental study in the pig.

The aim of this study was to investigate whether dysprosium (Dy) induced signal intensity (SI) loss in infarcted tissue in MR imaging. Myocardial infarction was induced in 12 pigs and Dy-DTPA-BMA (1.0 mmol/kg b.w.) was administered i.v. to 6 pigs 4 hours after occlusion and allowed to accumulate in the infarctions for 2 hours. Dy was analysed by inductively coupled plasma atomic emission spectrometry in infarcted and non-ischaemic tissue samples. The remaining 6 pigs, not administered contrast medium, served as controls. The infarctions demonstrated a high SI in the proton density- and T2-weighted sequences in both groups (ex vivo), although the Dy-DTPA-BMA group demonstrated a 3-fold greater concentration of Dy in infarcted compared with non-ischaemic myocardium. The lack of SI loss after Dy accumulation indicates that susceptibility effects are minor or absent in infarcted myocardium.

Contractile responses to electrolyte changes during coronary bolus perfusion. A comparative study in isolated rat, guinea pig, and rabbit hearts.

RATIONALE AND OBJECTIVES: The authors studied cardiac contractile responses during coronary bolus perfusion, as in coronary angiography, in three species and related the responses to the bolus content of electrolytes and to patterns of cardiac electrolyte regulation. METHODS: Isolated, paced hearts from the rat, guinea pig, and rabbit were subjected to coronary perfusion in the global mode with recording of left ventricular developed pressure during exposure (< 7.5 seconds) and recovery (30 seconds). RESULTS: In series 1 of the experiments, the perfusate reduction to one fifth of normal Ca, Na, K, Mg, and Ca/Na/K/Mg, and the removal of all ions, led to the following percentage changes in left ventricular developed pressure: rat -64, +84, -38, +7, +40, and +79; guinea pig -43, +48, +18, +5, +28, and +37; and rabbit -32, +60, +14, +4, +22, and +33. CONCLUSIONS: Except for K reduction, inducing negative inotropy in the rat but positive inotropy in the guinea pig and the rabbit, the three species responded similarly. Thus, changes in left ventricular developed pressure were related to changes in direction and rate of the sarcomal Na-Ca exchange. In series 2 of the experiments, iohexol (150 mg I/mL) +/- minor electrolyte additives were studied. Additives with Na 30 mmol/L only or with Na, Ca, K, and Mg carefully balanced reduced positive and negative inotropic responses in all three species.

Sodium-calcium relationships and cardiac function during coronary bolus perfusion.

The present review deals with the side-effects of contrast media (CM) on cardiac function during coronary angiography. A physiological approach is used to redefine existing concepts of CM osmotoxicity and chemotoxicity in terms of osmolal, ionic and molecular effects. The main idea conveyed is that purely ionic effects are of central importance during and immediately following the transit of a brief coronary bolus. Ionic effects result largely from rapid transient washout of normal extracellular ions, but are also influenced by ions present in the CM. In particular, the calcium (Ca) and sodium (Na) ions controlling cardiac function are easily affected. The myocardial Na-Ca exchange, which is mainly a physiological mechanism for cellular Ca efflux during cardiac relaxation, is therefore highlighted in detail. The importance of avoiding a potential Na-Ca mismatch is shown by examples from basic physiology, cardiac surgery and coronary angiography and by results of experiments with Visipaque. In the isomolal and isotonic CM Visipaque, which is based on the dimer isodixanol (320 mg I/ml), an available osmolal space is filled with an appropriately balanced supplement consisting of NaCl (19mM) and CaCl2 (0.3 mM).

Changes in contractile function with low-osmolal and isosmolal contrast media for coronary angiography.

Changes in contractile function induced by modern roentgen contrast media (CM) were examined in isolated rat hearts. Four coronary perfusions were undertaken in each heart with increasing volumes of each CM in order to test a wider spectrum of potential side-effects. Left ventricular developed pressure (LVDP) and heart rate (HR) were recorded. Six commercially available or investigational CM were examined: A, Hexabrix (ioxaglate 320 mg I/ml, Na 146 mM); B, Iosvist (iotrolan 300 mg I/ml, Na 6 mM);C, Visipaque (iodixanol 320 mg I/ml, Na 19 mM, Ca 0.3 mM); D, "Iodixanol high Ca-Mg" (iodixanol 320 mg I/ml, Na 19 mM, Ca 1.2 mM, Mg 0.6 MM); E, "Iohexol I 350" (iohexol 350 mg I/ml, Na 28 mM); and F, "Iohexol I 150" (iohexol 150 mg I/ml Na 28 mM). A, E and F were low-osmolal (400-940 mosm/kg H2O) CM whereas B, C and D were essentially isosmolal. Contractile changes (transient LVDP depression) was volume-dependent. Maximal values for LVDP depression were "Iohexol I 150" 11-22%

Early detection of regional myocardial ischemia in ex vivo piglet hearts: MR imaging with magnetization transfer.

The effects of regional myocardial ischemia and reperfusion on magnetization transfer (MT) contrast were investigated in an ex vivo perfused piglet heart model. The extent of the ischemic area was defined with perfusion magnetic resonance (MR) studies performed with use of extracellular contrast agents. Relative MT contrast was calculated for a total of 106 regions of interest in nine hearts. In the areas defined as being severely ischemic in the perfusion studies, a small but significant increase in the MT contrast of 18% +/- 9 (standard deviation) (n = 35) was found as early as 10 minutes after the start of ischemia. This contrast difference was reduced to 11% +/- 10 after 2 hours of total occlusion. The contrast between normal and ischemic tissue can be explained in part by the effect of inflowing blood, which leads to changes in both equilibrium magnetization and the apparent T1 of the perfused tissue. However, theoretical estimation suggests that these flow-related changes would produce a maximal relative change in MT contrast of approximately 4%. The most likely explanation for the rest of the observed changes is alteration in the distribution of cellular water related to the so-called intracellular edema that is known to be associated with the acute phase of myocardial ischemia.

Contrast-enhanced MR imaging of diffuse and focal splenic disease with use of magnetic starch microspheres.

The diagnostic value of magnetic starch microspheres (MSM), a new superparamagnetic contrast agent, was studied in experimental models of diffuse and focal splenic disease in rats by means of ex vivo relaxometry and in vivo magnetic resonance (MR) imaging. Owing to small differences in unenhanced T1 and T2 values between diffuse lymphoma and normal spleen, MR imaging failed to distinguish tumor-bearing animals from control animals by signal-to-noise ratios (SNRs) obtained with T1- and T2-weighted spin-echo sequences. One hour after injection of 20 mumol/kg MSM, lymphomatous spleen showed significantly (P < .001) reduced enhancement relative to normal splenic tissue. As a result, animals with diffuse lymphoma (SNR: 10.3 +/- 1.7) could be easily differentiated from control animals (SNR: 5.5 +/- 0.6) on T2-weighted (TR msec/TE msec = 2,000/45) images. In focal splenic disease, MSM produced normal enhancement of nontumorous splenic tissue, whereas relaxation times of tumors were not different before and after contrast agent injection. On T2-weighted images (2,000/45), the tumor-spleen contrast-to-noise ratio increased from 4.8 +/- 1.6 to 21.8 +/- 1.9 (+354%), improving conspicuity of splenic tumors. The results show that MSM-enhanced MR imaging improves the detection of diffuse and focal splenic disease.

Effect on cardiac contractile force from addition of cations and oxygen to iohexol. Comparison with other low-osmotic contrast media in the isolated rabbit heart during normal and reduced perfusion pressure.

The coronary arteries of the isolated rabbit heart were perfused with different contrast media (CM). The effects on cardiac contractile force (CF) from enriching iohexol solutions with sodium, calcium, potassium, magnesium and oxygen were investigated. The effects were studied during normal and reduced perfusion pressure; the latter was intended to simulate flow conditions distal to proximal stenotic processes of the coronary arteries. By adding the above mentioned cations to iohexol (175 mg I/ml) the smallest influence on CF was found when the CM contained 30 mM NaCl, 0.3 mM CaCl2, 0.9 mM KCl and 0.3 mM MgCl2 and this influence on CF was significantly less than caused by iohexol with 30 mM NaCl (p < or = 0.01). The influence on CF was further reduced when this iohexol solution was oxygenated with 100% oxygen (p < or = 0.001). This modified iohexol solution caused a significantly smaller influence on CF than the low-osmotic media iohexol, iopamiro, ioversol and ioxaglate (p < or = 0.001). Ioxaglate caused the greatest decrease in CF of all the CM (p < or = 0.001) and to a greater extent during reduced flow than during normal flow (p < or = 0.01). In conclusion, iohexol enriched with a balanced electrolyte solution and saturated with oxygen had a smaller adverse effect on contractility than iohexol, iopamidol, ioversol and ioxaglate.

K-space substitution: a novel dynamic imaging technique.

A rapid dynamic imaging sequence has been developed in which only the 32 phase encoding steps that encode low spatial frequencies are collected for each dynamic image. These are substituted into a previously acquired, 128 x 128 raw data set prior to image reconstruction. In this way the dynamic information is retained while the overall appearance is improved in comparison with images obtained by zero filling to 128 x 128, leading to better qualitative evaluation. The limited k-space sampling means that the technique is most effective for large homogeneous areas of signal change since fine changes in contrast are imperfectly recorded.

Reduced risk of ventricular fibrillation by balancing sodium, calcium, potassium and magnesium added to nonionic contrast media. An investigation in the isolated rabbit heart.

The effect of addition of calcium, potassium and magnesium to iohexol (350 mg I/ml) enriched with 30 mM sodium was investigated with regard to ventricular fibrillation (VF) in isolated rabbit hearts. Enriching iohexol containing 30 mM sodium with increasing amounts of calcium (0-1.2 mM) caused an increase in the frequency of VF. Increasing amounts of potassium (0-3.8 mM) to iohexol with 30 mM Na + 0.15 mM Ca + 0.1 mM Mg reduced the risk of VF. However, this protective effect of potassium on VF was reduced if magnesium was removed from the test solution. Furthermore, increasing amounts of magnesium (0-1.2 mM) to iohexol with 30 mM Na + 0.15 mM Ca + 0.4 mM K led to an increased frequency of VF. Iohexol with 30 mM Na + 0.3 mM Ca + 0.9 mM K + 0.3 mM Mg caused no VF. It is of interest to add multiple cations to sodium-containing nonionic media to improve cardiac contractility following coronary perfusion. The present study indicates that it is possible to enrich iohexol 350 mg I/ml + 30 mM Na with calcium, potassium and magnesium in small amounts, and balanced with respect to each ion, without changing the risk of VF.

Oral magnetic particles. Results from clinical phase II trials in 216 patients.

Oral magnetic particles (OMP) have been evaluated in a clinical phase II trial program comprising 216 patients in 7 European centers. Adult patients referred for MR imaging for various abdominal pathologies were examined. The patients received OMP at a concentration of 0.1 g/l (ultralow field) or 0.5 g/l (mid/high field) and OMP was diluted in water or in a more viscous liquid formulation. Depending on the area of interest, OMP was ingested in a volume of 300 to 800 ml. OMP was well tolerated with no serious adverse events and the patient acceptability was good. OMP had a good contrast effect on all applied pulse sequences. The viscous formulation of OMP was homogeneously distributed through the entire gastrointestinal tract without inducing disturbing susceptibility artifacts. The postcontrast diagnostic information was improved in 70% of the cases. Based on the encouraging results in phase II, OMP has been advanced to phase III clinical trials.

Sodium-calcium balance and cardiac function with isotonic iodixanol. An experimental study in the isolated rat heart.

RATIONALE AND OBJECTIVES: Three formulations of the nonionic dimer iodixanol (150/200/300 mg I/mL), made isotonic by the addition of NaCl (70/53/24 mM), were investigated regarding their potential for depressing cardiac contractility during coronary angiography. To maintain a stable cardiac function, the authors sought the requirements for the addition of a balanced amount of calcium (Ca). METHODS: Iodixanol 150, 200, and 300 mg I/mL were applied as a short-lasting bolus in isolated perfused rat hearts in the absence and presence of added Ca. The contractile function was assessed by measurement of changes in left ventricular developed pressure (LVDP). RESULTS: A transient LVDP depression was markedly alleviated by adding 0.2 to 0.4 mM Ca and almost abolished by 0.4 to 0.9 mM. Ca higher than 0.9 mM led to unstable hearts and too-extensive Ca loading. CONCLUSIONS: Caution should be used when adding Ca to iodixanol, particularly with sodium-calcium (Na-Ca) relationships. Appropriate Ca concentrations are probably 0.6 mM for iodixanol (150 mg I/mL); 0.4 to 0.6 mM for iodixanol (200 mg I/mL; and 0.4 mM for iodixanol (300 mg I/mL).

Effect of Gd-DTPA-BMA on magnetization transfer: application to rapid imaging of cardiac ischemia.

The addition of a paramagnetic contrast agent reduces the magnetization transfer effect between the free and restricted proton pools in both agar phantoms and cardiac muscle tissue. This reduction is due to the reduction in the intrinsic T1 of the free proton pool and increases the signal observed after a given magnetization transfer sequence. Images of ex vivo piglet hearts were obtained with a segmented snapshot FLASH (fast low-angle shot) sequence with a 128 x 128 matrix, four segments, and two signals averaged, resulting in an imaging time of 7 seconds. Magnetization transfer was induced by applying a DANTE (delays alternating with nutations for tailored excitations) pulse sequence in the intersegment interval. This was an efficient method of inducing magnetization transfer because it excites the restricted proton pool across the full frequency spectrum. Ischemia due to occlusion of the left anterior descending branch of the coronary artery could be visualized after infusion of gadolinium diethylenetriaminepentaacetic acid-bis(methylamide) (DTPA-BMA). Although the ischemia could be seen with the basic sequence, the contrast between ischemic and non-ischemic tissue improved when the magnetization transfer sequence was included. The most marked improvements in magnetization transfer were achieved with low doses of Gd-DTPA-BMA.

Iopentol in urography. A clinical comparison between iopentol and metrizoate including delayed reactions.

A double-blind comparative study of the nonionic contrast medium iopentol and the ionic contrast medium metrizoate for urography was carried out in 200 adult outpatients. Significantly less discomfort and other side effects were observed following iopentol than following metrizoate. No serious adverse reactions and no clinically significant alterations in heart rate or blood pressure were observed. A questionnaire was used to record delayed symptoms, from 30 min after contrast medium injection and for one week. The response rate was 92% and delayed adverse events were reported by 45%. The incidence of delayed reactions was significantly lower following iopentol than following metrizoate, i.e., delayed arm pain, fatigue, headache, diarrhea, nasal congestion, and rash. Delayed arm pain was probably due to contrast medium induced thrombosis in 1% following iopentol and in 8% following metrizoate. Most other symptoms were probably related to a combination of nocebo effect and coincidentally occurring symptoms. The urograms with both media were of similar high quality. Iopentol was found a suitable contrast medium for urography.