Peter Reimer

Cerebral MR perfusion imaging: First clinical application of a 1 M gadolinium chelate (Gadovist 1.0) in a double-blinded randomized dose-finding study†

The purpose of this study was to evaluate efficacy and safety of the 1 M gadolinium chelate Gadovist 1.0 for assessment of cerebral hemodynamics with dynamic susceptibility contrast‐enhanced magnetic resonance (MR) imaging. Eighty‐nine patients with carotid artery stenosis or cerebral infarcts were included in this multicenter, double‐blinded study using five dose groups from 0.1 to 0.5 mmol/kg. Imaging was performed with 1‐T scanners using a T2*‐weighted fast low‐angle shot (FLASH) sequence. Dose‐dependent changes in quantitative and qualitative parameters describing signal‐time curves and relative regional cerebral blood volume maps were investigated. For safety evaluation, vital signs, clinical and laboratory tests, and adverse events were assessed. The quantitative measurements revealed an optimal dose of 0.4 mmol/kg. The qualitative evaluation revealed that the required qualitative assessment for clinical purposes was already reached at a dose of 0.3 mmol/kg. No significant changes in vital signs and laboratory tests were found. No serious adverse events were observed. The combined results revealed the dose of 0.3 mmol/kg as the diagnostically adequate dose given the gradient‐echo sequence and field strength used. Gadovist 1.0 has been shown to be a safe and well‐tolerated contrast agent. J. Magn. Reson. Imaging 2000;12:371–380.

Clinical application of abdominal echoplanar imaging (EPI) : optimization using a retrofitted EPI system

Objective Echoplanar MRI (EPI) with data acquisition times as short as 36 ms has been advocated for imaging body areas where gross physiologic motion degrades images. In this study we investigated the effect of various operator-defined parameters on image quality in EPI of the abdomen using a commercially available scanner. Materials and Methods Specifically, we assessed the effect of breathholding, slice thickness, k-space coverage (raw data size), and high resolution EPI in volunteers. The effect of these parameters on signal-to-noise ratio (SNR) and image quality of liver, spleen, kidney, and pancreas was evaluated to propose guidelines for clinical EPI of the abdomen. The requirements for contiguous imaging were analyzed in a phantom experiment. Results Our study suggests that optimum clinical EPI requires a minimum slice thickness of 7 mm. Breathhold single shot techniques are preferred to avoid spatial misregistrations and to optimize the signal yield for segmented techniques. Maximum k-space coverage at a given TE should be implemented. High resolution techniques (128 ± 512) suffer from low SNR and are clinically not useful for routine EPI. Contiguous imaging requires a scan time of >6 s to eliminate effects of cross-talk. Conclusion The results suggest that clinical EPI requires careful attention to the choice of imaging parameters. The practical recommendations may help other investigators to optimize their clinical EPI studies.

Study of susceptibility-induced artefacts in GRASE with different echo train length

Abstract. The aim of this study was to evaluate the sensitivity of gradient-and-spin-echo (GRASE) sequences to susceptibility effects. GRASE sequences with 21 and 33 echoes per echo train were compared with a T2-weighted FSE sequence with an echo train length of 5 by means of MRI in phantoms, volunteers (n = 10), and patients (n = 19) with old hemorrhagic brain lesions. All experiments were performed on a 1.0-T clinical MR system (Impact Expert, Siemens AG, Erlangen, Germany) with constant imaging parameters. Contrast-to-noise ratios (CNRs) of tubes doped with iron oxides at different concentrations, of brain areas with physiological iron deposition (red nucleus, substantia nigra), and of areas of old brain hemorrhage were calculated for FSE and GRASE pulse sequences. Areas of old brain hemorrhage were also qualitatively analyzed for the degree of visible susceptibility effects by blinded reading. The CNR of iron oxide tubes and iron-containing brain areas decreased with increasing echo trains of GRASE sequences. The CNR of GRASE sequences decreased when compared with CNR of their FSE counterparts (GRASE 21 echo trains 23.8 ± 0.8, FSE 5 echo trains 26.7 ± 0.9; p≤ 0.01). Qualitative analysis confirmed these measurements. FSE with an ETL of 5 demonstrated significantly stronger susceptibility effects than their GRASE counterpart with an ETL of 21. The results demonstrate that GRASE sequences do not necessarily compensate for the reduced sensitivity of FSE to susceptibility effects. The complex signal behavior of GRASE makes conventional SE, gradient echo, or FSE sequences containing shorter echo trains preferable when patients with intracranial hemorrhage are clinically evaluated.

An organotypical in vitro model of the liver parenchyma for uptake studies of diagnostic MR receptor agents

Testing of receptor-specific MR contrast agents targeted to the liver is hampered by a shortage of viable in vitro models with in vivo-like hepatocellular morphology. Coated pits are ultrastructural signs of an active receptor mediated endocytosis in hepatocytes. Expression of coated pits by matrix overlaid hepatocytes was studied by transmission electron microscopy. Binding of a rhodaminated asialoglycoprotein receptor agent (MION-ASF-rh) was assessed by fluorescence microscopy. Fluorescence of cells exposed to MION-ASF-rh with D(+)-galactose reduced fluorescent light emission to a level of 58% of MION-ASF-rh-induced fluorescence. After preincubation with the hepatotoxin CCl4 a dose-dependent decrease in fluorescent light emission resulted. Hepatocytes maintained a homogeneous cell surface expression, with microprojections, coated pits, and vesicles on both sinusoidal surfaces. Matrix overlaid primary hepatocytes constitute a viable, morphologically and functionally differentiated model. This model can be used to study receptor binding, uptake, and blockage of diagnostic magnetopharmaceuticals under controlled conditions.

Evaluation of potential gastrointestinal contrast agents for echoplanar MR imaging

Although the diagnostic application of echoplanar imaging (EPI) has until now been limited, recent technical advances provide anatomic resolution and signal-to-noise ratios comparable to that of conventional MR imaging. The purpose of this study was to investigate approved aqueous gastrointestinal contrast agents for use in abdominal EPI. Conventional and echoplanar MR imaging experiments were performed with 1.0 Tesla whole body systems. Phantom measurements of Gastrografin, barium sulfate suspension, oral gadopentetate dimeglumine, water, and saline were performed. Signal intensity (SI) of aqueous oral barium sulfate and iodine based CT contrast agents was lower on conventional spin-echo (SE), Flash, and Turbo-Flash images than on EP images. The contrast agents exhibited higher SI on T2-weighted SE PE images and TI-time dependence on inversion recovery EP-images. The barium sulfate suspension was administered in volunteers to obtain information about bowel lumen enhancement and susceptibility artifacts. Oral administration of the aqueous barium sulfate suspension increased bowel lumen signal and reduced susceptibility artifacts. Approved aqueous gastrointestinal contrast media or flavored saline with long relaxation times may serve as safe, simple, and effective gastrointestinal contrast agents in abdominal EPI.

Application of a stable cell culture assay for the functional assessment of novel MR contrast agents

Abstract. The purpose of this study was to apply a new cell culture assay that preserves hepatocyte orientation and differentiation for screening of MR contrast agents with hepatocyte specificity. Cultured hepatocytes were sandwiched between two layers of collagen, preserving both hepatocyte function and morphology over a prolonged period of time. Plain and rhodaminated monocrystalline iron-oxide particles (MION and MION-rh) and asialoglycoprotein receptor-specific rhodaminated asialofetuin coupled to MION (MION-ASF-rh) were prepared. Dose-dependent competition experiments of these agents were performed with D( + )-galactose to determine the specificity of galactose-mediated cell uptake. To assess the impact of cell integrity on cell uptake dose-dependent functional experiments with two hepatotoxins (ethanol and CCl4) were performed. Normal cell cultures showed significantly higher fluorescent-light emission after incubation with hepatocyte-directed ASF-MION-rh than after incubation with MION-rh. Competition experiments of ASF-MION with galactose showed a dose-dependent decrease in calibrated fluorescent-light emission. Cell cultures treated with hepatotoxins demonstrated a dose-dependent reduction in calibrated fluorescent-light emission following incubation with ASF-MION-rh. The validated assay system allows assessment not only of hepatocyte specificity, but also of hepatocyte damage. Because the assay can be applied to cells from any species (rat, pig, human), it may represent an ideal test system prior to clinical trials of new hepatocyte-directed MR contrast agents.

Gadolinium-DTPA enhanced echoplanar MR imaging of the liver: Preliminary observations

This study describes our preliminary experience with dynamic gadopentetate dimeglumine enhanced echoplaner MR imaging (EPI) in fifteen patients with focal liver lesions. Lesion diagnosis was established by histology (n = 3) or typical imaging characteristics (exclusive of the EPI study) combined with clinical follow up (n = 12). Dynamic gadopentetate dimeglumine (0.1 mmol/kg) enhanced MR imaging was performed on a commercially available 1.5 T EPI equipped MR system using a single-excitation fat-suppressed inversion recovery pulse sequence. The choice of an IR sequence allowed nulling of the lesion signal by varying T1 prior to enhancement creating the optimal conditions for qualitative inspection of the enhancement profile. Intershot delay (defined as TR) ranged from 1-5s. Image analysis was performed qualitatively by two radiologists. Benign and malignant lesions displayed temporal enhancement profiles compatible with characteristic findings expected with conventional imaging modalities. Further refinements in our technique and expanded system capabilities will allow dynamic imaging of the entire liver with improved temporal resolution over conventional sequences.

Perfusionsuntersuchungen mit paramagnetischen Kontrastmitteln und schnellen Pulssequenzen bei zerebrovaskulären Erkrankungen und Hirntumoren

ZusammenfassungDie Kombination schneller MR-Sequenzen mit einer i. v. Bolusinjektion paramagnetischen Kontrastmittels liefert Informationen über die zerebrale Durchblutung, wobei mit der MR-Perfusionsuntersuchung primär das relative zerebrale Blutvolumen abgebildet wird. Ziel dieser Untersuchung war es, an einem klinischen MR-Tomographen zu prüfen, welche Informationen mit der MR-Perfusionsuntersuchung mit einer Standard-2D-FLASH-Sequenz bei Patienten mit zerebrovaskulären Erkrankungen und Tumoren zu erhalten sind. Bei Hirninfarkten, mikroangiopathischen Läsionen und sehr schlecht kollateralisierten Gefäßverschlüssen fanden sich Unterschiede zu den Normalpersonen in den MR-Perfusionsbildern. Unsere Ergebnisse zeigen, daß die Beschleunigung der Aufnahmesequenz, die Optimierung des Kontrastmittelbolus und optimierte Auswertung Voraussetzungen dafür sind, daß MR-Perfusionsuntersuchungen, die prinzipiell auch das absolute zerebrale Blutvolumen und den zerebralen Blutfluß bestimmen können, klinisch Einsatz finden werden.SummaryThe combination of fast MR sequences and rapid i. v. injection of paramagnetic contrast media provides information on cerebral perfusion. MR-perfusion imaging primarily depicts the relative cerebral blood volume. The aim of this study was to test whether MR-perfusion imaging with a clinical MR scanner using a standard 2D-FLASH sequence provides clinically relevant information on patients with cerebrovascular diseases and brain tumors. Brain infarctions, lesions in cerebral microangiopathy and occlusions of the carotid artery with very poor collateralization showed definite differences in perfusion imaging compared with normal controls. However, our results show that acceleration of the imaging sequence and optimization of the contrast bolus and data processing are prerequisites for the clinical use of this method, which in principle may provide information on the absolute cerebral blood volume and even blood flow.

Abdomen: Liver, Spleen, Biliary System, Pancreas, and GI Tract

Magnetic resonance imaging (MRI) is a widely used modality for the evaluation of diffuse liver disease and detection, as well as further characterization of focal liver disease. The same principles apply to the spleen. Furthermore, MRI represents a comprehensive approach for the biliary system, the pancreas, and the GI tract. The different technical options make MRI a useful but also challenging technique. MRI competes with ultrasound (US) and MDCT, which have also improved considerably.

MR Receptor Imaging of the Liver

Superparamagnetic iron oxides can be directed to specific organs and tissues for MR imaging by strategies such as receptor targeting. Targeting iron oxides to hepatocyte receptors rather then to liver macrophages allows delivery of a larger fraction of iron oxide to liver, increases tumor-liver contrast as most receptors are absent on malignant tumors, and allows the direct assessment of hepatocyte function. Thus receptor imaging represents a new dimension to the application of MR imaging. The feasibility of receptor imaging is shown in animal models of a) liver cancer, b) diffuse liver disease, and c) liver infarcts.