Safety and efficacy of reperfusion therapies in acute ischemic stroke related to left ventricular thrombus: A retrospective cohort study.

BACKGROUND: Left ventricular thrombus (LVT) is a source of cardiogenic embolic stroke. Conflicting data exist in the literature regarding the utilization of intravenous thrombolysis (IVT) at the acute phase of stroke in presence of LVT. We sought to assess the efficacy and safety of reperfusion therapies (IVT and/or thrombectomy) in patients with LVT. METHODS: We retrospectively analyzed patients with acute ischemic stroke and proven LVT and divided them in two groups: an intervention group with patients treated by reperfusion therapies and a control group with untreated patients. RESULTS: Between 2009 and 2021, 3890 patients were treated by reperfusion therapies in the Lyon stroke center, 33 of whom (0.9%) had LVT. We identified 27 control patients. There were more embolic recurrences at six months in the intervention group than in the control group (nine recurrences versus three, P=0.03, OR=13.56, 95% CI [1.5;195]). Only two early embolic recurrences (< 24h) occurred, both in the IVT group. There was a 4.8-fold decrease in the median NIHSS score between baseline and 24h follow-up in the intervention group (P<0.0001), and the two groups exhibited similar six-month mortality. At stroke onset, cardiopathy was known in 70% of patients, while LVT was known in 30%. CONCLUSION: Acute reperfusion therapies seem to be effective in the context of stroke in patients with LVT. However, further studies are needed to support the hypothesis that stroke recurrence might be related to the use of IVT.

Comparison of magnetic resonance angiography techniques to brain digital subtraction arteriography in the setting of mechanical thrombectomy: A non-inferiority study.

INTRODUCTION: We performed a non-inferiority study comparing magnetic resonance angiography (MRA) techniques including contrast-enhanced (CE) and time-of-flight (TOF) with brain digital subtraction arteriography (DSA) in localizing occlusion sites in acute ischemic stroke (AIS) with a prespecified inferiority margin taking into account thrombus migration. MATERIALS AND METHODS: HIBISCUS-STROKE (CoHort of Patients to Identify Biological and Imaging markerS of CardiovascUlar Outcomes in Stroke) includes large-vessel-occlusion (LVO) AIS treated with mechanical thrombectomy (MT) following brain magnetic resonance imaging (MRI) including both CE-MRA and TOF-MRA. Locations of arterial occlusions were assessed independently for both MRA techniques and compared to brain DSA findings. Number of patients needed was 48 patients to exclude a difference of more than 20%. Discrepancy factors were assessed using univariate general linear models analysis. RESULTS: The study included 151 patients with a mean age of 67.6±15.9years. In all included patients, TOF-MRA and CE-MRA detected arterial occlusions, which were confirmed by brain DSA. For CE-MRA, 38 (25.17%) patients had discordant findings compared with brain DSA and 50 patients (33.11%) with TOF-MRA. The discordance factors were identical for both MRA techniques namely, tandem occlusions (OR=1.29, P=0.004 for CE-MRA and OR=1.61, P<0.001 for TOF-MRA), proximal internal carotid artery occlusions (OR=1.30, P=0.002 for CE-MRA and OR=1.47, P<0.001 for TOF-MRA) and time from MRI to MT (OR=1.01, P=0.01 for CE-MRA and OR=1.01, P=0.02 for TOF-MRA). CONCLUSION: Both MRA techniques are inferior to brain DSA in localizing arterial occlusions in LVO-AIS patients despite addressing the migratory nature of the thrombus.

Multifocal arterial wall contrast - enhancement in ischemic stroke: A mirror of systemic inflammatory response in acute stroke.

PURPOSE: Intracranial plaque gadolinium enhancement revealed by high-resolution MRI imaging (HR MRI) is considered as a marker of plaque inflammation, a contributing factor of plaque unstability. The aim of the present study was to assess the distribution of gadolinium enhancement in intracranial atherosclerosis. METHODS: Single center analysis of ischemic stroke patients with intracranial atherosclerotic stenosis of M1 or M2 segments of middle cerebral artery, or terminal internal carotid artery (ICA) based on CT-angio or MR-angio. High-resolution MRI imaging (HRMRI) was performed within 6 first weeks following the index event, with 3DT2 BB (black-blood) and 3D T1 BB MR sequences pre and post-contrast administration. RESULTS: We identified 8 patients with 14 plaques, 4 were deemed non-culprit and 10 culprit. All culprit plaques (10/10 plaques) and 3 out of 4 non-culprit plaques showed a gadolinium enhancement. CONCLUSION: At the acute/subacute stage of stroke, a gadolinium enhancement may affect multiple asymptomatic intracranial plaques and may reflect a global inflammatory state.

Combined analysis of MGMT methylation and dynamic-susceptibility-contrast MRI for the distinction between early and pseudo-progression in glioblastoma patients.

INTRODUCTION: Currently, no single diagnostic modality allows the distinction between early progression (EP) and pseudo-progression (Psp) in glioblastoma patients. Herein we aimed to identify the characteristics associated with EP and Psp, and to analyze their diagnostic value alone and in combination. MATERIAL AND METHODS: We reviewed the clinical, conventional magnetic resonance imaging (MRI), and molecular characteristics (MGMT promoter methylation, IDH mutation, and EGFR amplification) of glioblastoma patients who presented an EP (n=59) or a Psp (n=24) within six months after temozolomide radiochemotherapy. We analyzed relative cerebral blood volume (rCBV) and relative vessel permeability on K2 maps (rK2) in a subset of 33 patients using dynamic-susceptibility-contrast MRI. RESULTS: In univariate analysis, EP was associated with neurological deterioration, higher doses of dexamethasone, appearance of a new enhanced lesion, subependymal enhancement, higher rCBV and rK2 values. Psp occurred earlier after radiotherapy completion and was associated with IDH1 R132H mutation, and MGMT methylation. In multivariate analysis, rCBV, rK2, and MGMT methylation status were independently associated with EP and Psp. All patients with a methylated MGMT promoter and a low rCBV (<1.75) were classified as Psp while all patients with an unmethylated MGMT promoter and a high rCBV (≥1.75) were classified as EP. Among patients with discordant MGMT methylation and rCBV characteristics, higher rK2 values tended to be associated with EP. CONCLUSION: Combined analysis of MGMT methylation, rCBV and vessel permeability on K2 maps seems helpful to distinguish EP from Psp. A prospective study is warranted to confirm these results.

Whole-body MRI with diffusion-weighted sequences compared with 18 FDG PET-CT, CT and superficial lymph node ultrasonography in the staging of advanced cutaneous melanoma: a prospective study.

OBJECTIVES: The aim of our study was to compare the diagnostic performances of non-radiating whole-body magnetic resonance imaging (wbMRI), either volumetric, with Volumetric interpolated breath-hold examination (VIBE) or metabolic, with diffusion-weighted sequences (wbMRI), with classical irradiating techniques such as PET-CT, CT and with lymph node ultrasonography (US) for the staging of advanced melanoma. PATIENTS AND METHODS: Thirty-seven melanoma AJCC stage IV patients were prospectively included. All images were independently interpreted without prior knowledge of the results of studies performed with concurrent techniques, and all imaging techniques were scheduled within a mean interval of 7 days. The overall and site-specific diagnosis performances of each imaging modality were studied, as well as the interest of combined MRI VIBE and diffusion sequences. RESULTS: The number of visceral or lymph node metastases spotted was, respectively, 218, with 125 metastases for wbMRI, 191/103 for PET-CT, 209/115 for CT and 33/13 for lymph node US. No statistically significant difference (P < 0.05) of overall diagnostic performances between wbMRI (Se 84%, Sp 87.1%, PPV 89.8%, NPV 80.2%) and PET-CT (Se 79.8%, Sp 93.1%, PPV 93.2%, NPV 79.4%) was observed. No statistically significant difference was found between wbMRI and PET-CT with two channels for CT with respect to different metastatic sites. Compared with the CT, wbMRI had significantly better overall specificity (P = 0.0011) and PPV (P = 0.02). For lung exploration, sensitivity of wbMRI (51.6%) was inferior to CT (71.4%). To detect superficial metastatic lymph nodes, wbMRI and US both showed high diagnostic accuracy with no statistically significant difference. Intra-observer agreement was almost perfect for all imaging modalities considering the overall staging. Inter-observer agreement for wbMRI and diffusion alone was almost perfect except for bone and lymphatic sites. Overall diagnostic performance of diffusion alone was significantly inferior to those of combined VIBE and diffusion sequences. CONCLUSIONS: Whole-body MRI, using diffusion weighted sequences, was a reliable non-radiating imaging for staging of melanoma and offers the same diagnostic performances than combined CT, PET-CT and lymph node US.

Early Detection of Underlying Cavernomas in Patients with Spontaneous Acute Intracerebral Hematomas.

BACKGROUND AND PURPOSE: Early identification of the etiology of spontaneous acute intracerebral hemorrhage is essential for appropriate management. This study aimed to develop an imaging model to identify cavernoma-related hematomas. MATERIALS AND METHODS: Patients 1-55 years of age with acute (≤7 days) spontaneous intracerebral hemorrhage were included. Two neuroradiologists reviewed CT and MR imaging data and assessed the characteristics of hematomas, including their shape (spherical/ovoid or not), their regular or irregular margins, and associated abnormalities including extralesional hemorrhage and peripheral rim enhancement. Imaging findings were correlated with etiology. The study population was randomly split to provide a training sample (50%) and a validation sample (50%). From the training sample, univariate and multivariate logistic regression was performed to identify factors predictive of cavernomas, and a decision tree was built. Its performance was assessed using the validation sample. RESULTS: Four hundred seventy-eight patients were included, of whom 85 had hemorrhagic cavernomas. In multivariate analysis, cavernoma-related hematomas were associated with spherical/ovoid shape (P < .001), regular margins (P = .009), absence of extralesional hemorrhage (P = .01), and absence of peripheral rim enhancement (P = .002). These criteria were included in the decision tree model. The validation sample (n = 239) had the following performance: diagnostic accuracy of 96.1% (95% CI, 92.2%-98.4%), sensitivity of 97.95% (95% CI, 95.8%-98.9%), specificity of 89.5% (95% CI, 75.2%-97.0%), positive predictive value of 97.7% (95% CI, 94.3%-99.1%), and negative predictive value of 94.4% (95% CI, 81.0%-98.5%). CONCLUSIONS: An imaging model including ovoid/spherical shape, regular margins, absence of extralesional hemorrhage, and absence of peripheral rim enhancement accurately identifies cavernoma-related acute spontaneous cerebral hematomas in young patients.

FLAIR Vascular Hyperintensities as a Surrogate of Collaterals in Acute Stroke: DWI Matters.

BACKGROUND AND PURPOSE: FLAIR vascular hyperintensities are thought to represent leptomeningeal collaterals in acute ischemic stroke. However, whether all-FLAIR vascular hyperintensities or FLAIR vascular hyperintensities-DWI mismatch, ie, FLAIR vascular hyperintensities beyond the DWI lesion, best reflects collaterals remains debated. We aimed to compare the value of FLAIR vascular hyperintensities-DWI mismatch versus all-FLAIR vascular hyperintensities for collateral assessment using PWI-derived collateral flow maps as a reference. MATERIALS AND METHODS: We retrospectively reviewed the registries of 6 large stroke centers and included all patients with acute stroke with anterior circulation large-vessel occlusion who underwent MR imaging with PWI before thrombectomy. Collateral status was graded from 1 to 4 on PWI-derived collateral flow maps and dichotomized into good (grades 3-4) and poor (grades 1-2). The extent of all-FLAIR vascular hyperintensities and FLAIR vascular hyperintensities-DWI mismatch was assessed on the 7 cortical ASPECTS regions, ranging from 0 (absence) to 7 (extensive), and associations with good collaterals were compared using receiver operating characteristic curves. RESULTS: Of the 209 included patients, 133 (64%) and 76 (36%) had good and poor collaterals, respectively. All-FLAIR vascular hyperintensity extent was similar between collateral groups (P = .76). Conversely, FLAIR vascular hyperintensities-DWI mismatch extent was significantly higher in patients with good compared with poor collaterals (P < .001). The area under the curve was 0.80 (95% CI, 0.74-0.87) for FLAIR vascular hyperintensities-DWI mismatch and 0.52 (95% CI, 0.44-0.60) for all-FLAIR vascular hyperintensities (P < .001 for the comparison), to predict good collaterals. Variables independently associated with good collaterals were smaller DWI lesion volume (P < .001) and larger FLAIR vascular hyperintensities-DWI mismatch (P = .02). CONCLUSIONS: In acute ischemic stroke with large-vessel occlusion, the extent of FLAIR vascular hyperintensities does not reliably reflect collateral status unless one accounts for DWI.

Quantitative effects of cell internalization of two types of ultrasmall superparamagnetic iron oxide nanoparticles at 4.7 T and 7 T.

PURPOSE: MRI coupled with the intravenous injection of ultrasmall superparamagnetic particles of iron oxides (USPIOs) is a promising tool for the study of neuroinflammation. Quantification of the approximate number of magnetically labelled macrophages may provide an effective and efficient method for monitoring inflammatory cells. The purpose of the present study was to characterise the relaxation properties of macrophages labelled with two types of USPIOs, at 4.7 T and 7 T. METHODS: USPIO-labelled bone-marrow-derived macrophage phantoms were compared with phantoms of free dispersed USPIOs with the same global iron concentration, using multi-parametric (T1, T2 and T2) quantitative MRI. The same protocol was then evaluated in living mice after intracerebral injection of iron-labelled macrophages vs free iron oxide. RESULTS: A linear relationship was observed among R1, R2 and R2 values and iron concentration in vitro at 4.7 T and at 7 T. At a given field, T1 and T2 relaxivities of both types of USPIOs decreased following internalisation into macrophages, while T2 relaxivities increased. CONCLUSION: There was fair overall agreement between the theoretical number of injected cells and the number estimated from T2 quantification and in vitro calibration curves, supporting the validity of the present in vitro calibration curves for in vivo investigation.

Imaging inflammation in stroke using magnetic resonance imaging.

Stroke is the third leading cause of death, after myocardial infarction and cancer, and the leading cause of permanent disability in Western countries. Although anti-inflammatory drugs have shown very promising results in preclinical rodent studies, they appeared to be ineffective against stroke in clinical trials. In this context, non-invasive detection of inflammatory cells after brain ischemia could be helpful (i) to select patients who may benefit from anti-inflammatory treatment, and/or (ii) to target an adequate individualized therapeutic time window. Magnetic resonance imaging (MRI) coupled with injection of iron oxide nanoparticles, a contrast agent taken up by macrophages ex vivo and in vivo, appears to be a promising tool for this purpose. This review focuses on the use of this technique to image inflammation in pre-clinical and clinical studies of stroke. Despite current limitations, MRI of inflammation may become an important tool for the investigation of novel ischemic stroke therapeutics targeting inflammation.

Imagery of pineal tumors.

Pineal tumors are rare and include a large variety of entities. Germ cell tumors are relatively frequent and often secreting lesions. Pineal parenchymal tumors include pineocytomas, pineal parenchymal tumor of intermediate differentiation, pineoblastomas and papillary tumors of the pineal region. Other lesions including astrocytomas and meningiomas as well as congenital malformations i.e. benign cysts, lipomas, epidermoid and dermoid cysts, which can also arise from the pineal region. Imagery is often non-specific but detailed analysis of the images compared with the hormone profile can narrow the spectrum of possible diagnosis.

Baseline magnetic resonance imaging parameters and stroke outcome in patients treated by intravenous tissue plasminogen activator.

BACKGROUND AND PURPOSE: We designed a prospective sequential pretreatment and posttreatment MRI study to assess the relation between neuroimaging parameters and clinical outcome in patients treated with intravenous recombinant tissue-type plasminogen activator (rtPA). METHODS: Patients with symptoms of acute hemispheric ischemic stroke were recruited. The National Institutes of Health Stroke Scale (NIHSS) score was assessed at baseline and at days 1, 7, and 60, and the modified Rankin scale (mRS) at day 60, by which outcome was classified in terms of independence (mRS score 0, 1, or 2) or severe disability or death (mRS score 3 through 6), was assigned. Multimodal stroke MRI was performed at presentation and repeated at day 1. MRI procedures included magnetic resonance angiography, T2* gradient-echo sequence, echoplanar imaging, and isotropic diffusion- (DWI) and perfusion-weighted (PWI) imaging. Patients were treated with intravenous rtPA after MRI completion. RESULTS: Twenty-nine patients (16 men and 13 women; mean+/-SD age, 65+/-14 years) underwent MRI; the mean time from symptom onset to treatment was 255+/-62 minutes. Twenty-six patients had a vessel occlusion, and 15 patients experienced a partial (Thrombolysis in Myocardial Infarction [TIMI]-2) or total (TIMI-3) recanalization at day 1, whereas 11 patients had a persistent occlusion. Mean NIHSS scores at day 60 were 5.7+/-5.4 if recanalization had occurred and 14+/-2 in cases of persistent occlusion. According to the mRS, 13 patients were independent (mRS 0 through 2), whereas severe disability or death (mRS 3 through 6) was observed in 15 patients. A better outcome was observed when recanalization was achieved (r=-0.68, P=0.0002). PWI volume and time to peak (TTP) within the DWI lesion assessed before therapy were correlated with day-60 NIHSS score (PWI volume: r=0.51, P=0.006, TTP: r=0.35, P=0.07). The day-0 DWI abnormality volume was well correlated with day-60 NIHSS score (r=0.58, P=0.001). Multiple regression linear analysis showed that 2 factors mainly influenced clinical outcome: (1) recanalization, with a high correlation with NIHSS score at day 60 (P=0.0001) and (2) day-0 DWI lesion volume, which is closely associated with day-60 NIHSS score (P=0.03). CONCLUSIONS: Baseline DWI volume and recanalization are the main factors influencing clinical outcome after rtPA for ischemic stroke.

rtPA intravenous thrombolysis in anterior choroidal artery territory stroke.

OBJECTIVE: To study the possible specific response to recombinant tissue plasminogen activator (rtPA) thrombolysis of anterior choroidal artery (AChA) stroke. BACKGROUND: Outcome and response after rtPA thrombolysis are possibly better in small-vessel infarcts, but a specific study of AChA stroke has not yet been performed. METHODS: The authors proposed an open trial of IV rtPA within 7 hours in patients age 20 and 81 years with all types of internal carotid artery territory stroke if the baseline Scandinavian Stroke Scale (SSS) score was less than 48. A dose of rtPA 0.8 mg/kg was infused over 90 minutes. Of 114 consecutive patients, 9 patients (7.9%) exhibited hypodensity in the AChA territory on day 1 brain CT. RESULTS: Seven of nine patients with AChA infarct had a primary early recovery within 6 hours after the initiation of rtPA infusion. In addition, recovery was complete in five patients and partial in two patients. No intracerebral hematoma was observed. Three patients had a "reinfarct syndrome" at 12, 25, and 48 hours respectively. However, in the two latter patients treated with IV heparin, the deficit disappeared again with the increase of heparin dose in one patient and disappeared spontaneously in the other patient. The overall outcome at day 90 was six total recoveries in nine patients (66%). Patients with a final good outcome had a slight "unstructured" hypodensity in the AChA territory on day 1 brain CT, whereas patients with a bad outcome had the classic "structured" hypodensity of AChA territory stroke. CONCLUSION: These data support a specific quick response of AChA territory stroke to IV rtPA thrombolysis, probably due to the small size of the artery and of the "clot." The high frequency of the reinfarct syndrome is a clinical fact that is difficult to explain. Efficient heparin treatment after 24 hours may control the reinfarct syndrome in some patients.

Gadolinium-ethoxybenzyl-DTPA, a new liver-specific magnetic resonance contrast agent. Kinetic and enhancement patterns in normal and cholestatic rats.

OBJECTIVES: Gadolinium-ethoxybenzyl-DTPA (Gd-EOB-DTPA) is a new hepatobiliary magnetic resonance imaging (MRI) contrast agent with a dual elimination: 70% via the liver and bile and 30% via the kidney in normal rats. The abdominal enhancement patterns of this new compound and the uptake mechanism by the liver were studied in rats using tissue relaxometry and MRI. METHODS: Twelve normal rats, 33 rats treated with agents designed to inhibit biliary excretion of the agent, and 6 rats with surgically ligated common bile ducts received Gd-EOB-DTPA intravenously. Distribution and excretion were measured by MR relaxometry. MR signal intensity was measured over time for liver, kidney, and bowel. RESULTS: In normal animals, 0.1 mmol/kg Gd-EOB-DTPA induced a significantly greater (200%) and more prolonged liver signal enhancement (100% at 30 minutes) than Gd-DTPA at the same dose. Either hyperbilirubinemia, induced by common bile duct ligation, or bromosulfophtalein (BSP) infusion inhibited liver uptake of Gd-EOB-DTPA, resulting in a preferential elimination via the kidney. Taurocholate (TC), an inhibitor of the bile acid transporter, was unable to block the liver uptake of Gd-EOB-DTPA. Blood half-lives of Gd-EOB-DTPA in rats were 2.4 minutes for the first component and 8.2 minutes for the second. CONCLUSIONS: Data indicate that transport of Gd-EOB-DTPA through the liver into bile is driven by the organic anion transporter. The relation between enhancement of liver and kidney may be diagnostically useful to indirectly evaluate liver excretory function. Yet, persistent enhancement of liver, even in the presence of severe hyperbilirubinemia, should be sufficient to identify focal mass lesions.

CT pulmonary angiography with a macromolecular contrast medium: a comparative study versus iobitridol in rabbits.

RATIONALE AND OBJECTIVES: To compare the pharmacokinetics of a new macromolecular iodinated contrast medium, prototype P743, with a standard contrast agent (iobitridol) for spiral computed tomography pulmonary angiography in rabbits. METHODS: Manual injection was first used to test the performance of P743 even in cases of nonoptimal bolus timing. Then a protocol was designed to compare vessel enhancement in both first-pass and delayed scans for the two contrast agents with the help of a power injector. RESULTS: With manual fast injection, the first pass of iobitridol was observed only on proximal scans. Conversely, opacification of vessels was maintained during three spiral scans with P743 under the same injection conditions. When optimal bolus timing was performed, higher vessel enhancement was observed during bolus first pass with iobitridol (iodine dosage 250 mg I/kg) compared with P743 (150 mg I/kg). However, during the postbolus phase, the decrease in attenuation values was markedly faster with iobitridol than with P743. CONCLUSIONS: This study confirmed that P743 remains more intravascular than iobitridol, which may have clinical implications for the diagnosis of pulmonary embolism, for example.

Lung perfusion demonstrated by contrast-enhanced dynamic magnetic resonance imaging. Application to unilateral lung transplantation.

RATIONALE AND OBJECTIVES: The authors evaluate the use of magnetic resonance (MR) to image pulmonary perfusion in healthy controls and to detect pulmonary defects in patients with unilateral lung transplantation, using dynamic images after contrast administration. METHODS: Five patients with right lung transplantation and nine healthy volunteers underwent MR imaging. Twenty-five subsecond contrast-enhanced MR images (turbo-fast low-angle shot [FLASH]) were obtained at the level of the pulmonary arteries after a single injection of gadopentetate dimeglumine (0.1 mmol/kg) in an antecubital vein. Perfusion lung scintigraphy was done within 24 hours after the MR imaging examination in the transplanted patients. RESULTS: Before administration of contrast material, MR images showed both lungs to be homogeneous and of low signal intensity in healthy controls and in patients with lung transplantation. After contrast administration in controls, the mean signal intensity of the dependent lung increased markedly to 171 +/- 24% above baseline, whereas the nondependent signal intensity lung increased by only 105 +/- 17%; these changes were significantly different. In all patients with lung transplantation, a clear perfusion defect was demonstrated in the native lung. This defect was confirmed in all cases by perfusion nuclear scintigraphy, which showed that the majority of lung perfusion is directed to the transplanted allograft, compared with the native contralateral lung. CONCLUSIONS: Our results suggest that dynamic contrast-enhanced MR imaging is a potential method for detecting pulmonary perfusion defects in patients with lung transplantation.

Magnetic resonance imaging detection of an experimental pulmonary perfusion deficit using a macromolecular contrast agent. Polylysine-gadolinium-DTPA40.

RATIONALE AND OBJECTIVES: This study was designed to evaluate the potential of a blood-pool magnetic resonance (MR) contrast agent, polylysine-gadolinium-DTPA40 (polylysine-Gd-DTPA40) for detecting pulmonary perfusion defects. MATERIALS AND METHODS: Pulmonary emboli were induced in 10 rats by venous injection of 0.2 mL of air. Axial spin-echo images were acquired (TR = 800 mseconds; TE = 6 mseconds) before and after air injection and serially after the administration of polylysine-Gd-DTPA40. The embolism model was confirmed by scintigraphy using 99mTc-macroaggregated albumin. RESULTS: Signal intensity differences between normal and embolized lungs before and after the air injection were less than 25%. After polylysine-Gd-DTPA40 administration, signal intensity of the perfused lung increased more than 200%, whereas the embolized lung increased by only 25%. Signal intensities of the perfused lung remained stable for 1 hour, whereas signal intensities of the embolized lung gradually increased for 20 minutes as the air embolus dissolved. CONCLUSION: Magnetic resonance imaging (MRI) enhanced with a macromolecular blood-pool contrast agent can be used to detect acute pulmonary embolism in a confirmed animal model.

Magnetic resonance imaging demonstration of pharmacologic-induced myocardial vasodilatation using a macromolecular gadolinium contrast agent.

RATIONALE AND OBJECTIVES: Adenosine is a potent vasodilator used clinically in nuclear scintigraphy to assess coronary artery reserves. The potential to identify this vasodilating effect of adenosine using magnetic resonance imaging (MRI), which is superior in spatial resolution to nuclear scintigraphy, combined with a blood-pool MRI contrast agent, was investigated in normal rats. METHODS: Groups of Sprague-Dawley rats received successive infusions of either adenosine (3 mg/kg/minute; n = 7) or dipyridamole (negative control; up to 1.0 mg/kg/minute; n = 9), both before and after contrast enhancement, with a macromolecular blood-pool MRI contrast agent, albumin-gadolinium-DTPA35 (Gd-DTPA35) (4.0 mumol Gd per kilogram). Electrocardiographically (ECG) gated MRIs (2.0 Tesla), acquired serially before and after contrast enhancement, and with and without either adenosine or dipyridamole infusions, to monitor potential pharmacologic responses. RESULTS: During repeated infusions of adenosine, the postcontrast myocardial enhancement, reflecting blood volume, increased significantly (P < .05), up to 150%, compared with pre-adenosine enhancement. Infusions of dipyridamole, pharmacologically inactive in rats, produced no change in myocardial enhancement. CONCLUSIONS: The increased myocardial signal intensity observed during adenosine infusions after enhancement of the blood pool can be attributed to increased blood volume accompanying coronary vasodilatation. The method, which does not require a continuous infusion of contrast agent, has potential for the clinical evaluations of coronary artery reserves.

Gadolinium-ethoxybenzyl-DTPA, a new liver-directed magnetic resonance contrast agent. Absence of acute hepatotoxic, cardiovascular, or immunogenic effects.

RATIONALE AND OBJECTIVES: Gadolinium-ethoxybenzyl-DTPA (Gd-EOB-DTPA) is a recently introduced experimental magnetic resonance (MR) contrast agent for hepatic imaging. Although liver enhancement has been investigated in a number of animal models, tolerance evaluations of Gd-EOB-DTPA injection have been limited. METHODS: The authors investigated acute hepatotoxicity in an isolated perfused rat liver model, cardiovascular effects in the anesthetized rat, and potential immunogenicity of Gd-EOB-DTPA using detection of specific antibodies. RESULTS: Using perfused rat liver model, no significant deviation could be observed for functional parameters, liver enzymes, or potassium release, comparing Gd-EOB-DTPA to a control, but there was a significant choleresis (+250% bile flow). Hemodynamic effects of Gd-EOB-DTPA were observed after femoral bolus injection, but only with relatively high dosages (0.3-0.5 mmol/kg, 10-fold the likely clinical dose in humans). Experimental conditions, idealized for antibody induction, failed to cause an IgG immune response to Gd-EOB-DTPA in the intact rat. CONCLUSIONS: The results further support preliminary conclusions that Gd-EOB-DTPA is a well-tolerated MR contrast agent.