Karl-Jürgen Wolf

Magnetic resonance imaging of atherosclerotic plaques using superparamagnetic iron oxide particles

Experimental data show accumulation of superparamagnetic iron oxide (SPIO) particles in atherosclerotic plaques. SPIO uptake occurred in plaques, suggesting an increased endothelial permeability and macrophage infiltrates as signs of inflammatory plaque activity. We incidentally observed SPIO uptake in aortic and arterial wall segments in patients who had originally received the magnetic resonance (MR) contrast agent for staging lymph node metastases. Twenty patients (19 male, 1 female; mean age, 64; range, 41–78 years) with bladder or prostate cancer underwent MR imaging (MRI) using a T2*‐weighted high‐resolution gradient‐echo sequence prior to and 24–36 hours after intravenous injection of 2.6 mg of Fe/kg of SPIO (Sinerem®). The aorta, both common external and internal iliac, as well as both superficial femoral arteries, were retrospectively analyzed for atherosclerotic wall changes. One patient was excluded. A positive finding was defined as an area of pronounced signal loss on postcontrast images clearly confined to the arterial wall, which was absent in the precontrast examination or increased in size. Such a finding was observed in one to three arteries in 7 of the 19 patients. The pronounced signal loss in the wall of the aorta and pelvic arteries seen in part of an elderly patient population after intravenous SPIO administration strongly suggests that this contrast agent accumulates in human atherosclerotic plaques. J. Magn. Reson. Imaging 2001;14:355–361.

fMRI assessment of somatotopy in human Brodmann area 3b by electrical finger stimulation

FUNCTIONAL magnetic resonance imaging (fMRI) is capable of detecting focal brain activation induced by electrical stimulation of single fingers in human subjects. In eight subjects somatotopic arrangement of the second and fifth finger was found in Brodmann area 3b of the primary somatosensory cortex. In four subjects the representation area of the second finger was located lateral and inferior to the fifth finger; in one subject the somatotopy was reversed. In three subjects representation areas of the two fingers in Brodmann area 3b were found overlapping. Additional activated areas were found on the crown of ipsilateral and contralateral post-central gyrus (Brodmann areas 1 and 2) and posterior parietal cortex.

Detection and Characterisation of Liver Metastases

Modern liver imaging of cancer patients requires an imaging modality that is not only highly sensitive in detecting lesions but also provides reliable characterisation of lesions and thus allows differentiation of metastases from frequently found benign lesions. Conventional ultrasound (US) has a relatively poor sensitivity and specificity for imaging liver metastases and US used to be inferior to CT and MRI mainly due to a lack of contrast agents. This has changed with the advent of microbubble contrast agents for US. The use of recent contrast agents such as SonoVue (Bracco, Italy) combined with low mechanical index contrast-specific imaging techniques such as Contrast Pulse Sequencing provides dynamic real time imaging of focal liver lesions in the arterial, portal venous and delayed phase. This improves lesion detection and characterisation. To investigate the benefit of SonoVue for detecting liver metastases we studied 40 cancer patients with liver lesions on reference imaging (CT or MRI), 37 of them had metastases. The mean number of reference confirmed metastases per patient increased from 1.85+/-1.79 on conventional ultrasound to 2.73+/-2.50 post SonoVue (p < 0.05). CEUS showed more individual metastases than baseline in 12 (34%) patients. Using CT or MRI as the reference, the mean sensitivity to individual metastases increased from 69% on baseline US to 90% post contrast (p < 0.0005). The role of SonoVue in characterisation of focal liver lesions was evaluated in 63 patients. One lesion was studied per patient. Based on standardised dynamic enhancement criteria for each lesion type, the number of correctly diagnosed lesions improved from 41 (65%) on baseline US to 58 (92%) post contrast (p < 0.001). On CEUS all 27 metastases were correctly diagnosed, while baseline US misinterpreted 2 of these. The number of correctly diagnosed benign lesions (n = 28) increased from 12 (43%) on baseline to 25 (89%) post SonoVue. In conclusion, detection and characterisation of focal liver lesions by US are markedly improved by the use of SonoVue. Contrast agents add a new dimension to sonography allowing it to rival CT and MRI, especially for lesion characterisation.

Qualitative and Quantitative Evaluation of Hepatocellular Carcinoma and Cirrhotic Liver Enhancement Using Gd-EOB-DTPA

OBJECTIVE The objective of our study was to prospectively evaluate quantitatively and qualitatively the enhancement patterns of cirrhotic liver tissue and hepatocellular carcinoma (HCC) after administration of the hepatocyte-specific contrast agent gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) on dynamic MRI and to determine the time point of maximum liver-to-lesion contrast. SUBJECTS AND METHODS Twenty-five patients with HCC in liver cirrhosis underwent 1.5-T MRI. T2-weighted turbo spin-echo and T1-weighted 3D gradient-echo sequences before and between 15 seconds and 20 minutes after the injection of 10 mL of Gd-EOB-DTPA were performed. Signal-to-noise ratios (SNRs) of liver parenchyma and liver-to-lesion contrast-to-noise ratios (CNRs) were calculated and plotted over time. Enhancement patterns of HCC were characterized qualitatively by two radiologists. RESULTS The SNR of liver parenchyma increased significantly at 15 seconds and 60 seconds after contrast injection and remained stable thereafter. HCC showed positive CNR during the arterial phase and increasingly negative CNR during the further time course (p < 0.05). The maximum absolute CNR was found at 20 minutes after contrast injection. There was no correlation between the degree of enhancement at any time point and tumor grade. On qualitative evaluation, 16 HCCs showed arterial enhancement with early washout, and five showed arterial enhancement with late washout. In the remaining four HCCs, enhancement persisted until 20 minutes. Lesion conspicuity at 20 minutes after contrast injection was at least equal to or higher than it was on the remaining sequences in 19 of the 25 patients. CONCLUSION After Gd-EOB-DTPA injection, most HCCs showed typical arterial enhancement with early washout. Liver-to-lesion contrast was best at 20 minutes.

A new concept for melatonin deficit: on pineal calcification and melatonin excretion.

Even though exogenous melatonin has proven to influence sleep and circadian parameters, low endogenous melatonin is not related to sleep disturbances, nor does it predict response to melatonin replacement therapy. In this manuscript, we present a new concept towards a definition of a melatonin deficit. The purpose of the study was to introduce a marker for an intra-individual decrease in melatonin production. Therefore, we developed a method to quantify the degree of pineal calcification (DOC) using cranial computed tomography. Combining pineal DOC with the organss size, we estimated the uncalcified pineal gland volume. This estimation was positively and significantly associated with 6-sulfatoxymelatonin (aMT6s), collected over 24 hours in urine, in 26 subjects. Data yielded evidence that the decline in aMT6s excretion with age can be sufficiently explained by an increased pineal calcification. These results suggest that DOC might be useful as an indicator of an intra-individual, decreased capability of the pineal gland to produce melatonin. DOC might prove to be a response-marker for melatonin replacement therapy and a vulnerability marker of the circadian timing system.

Magnetic resonance imaging-controlled laser-induced interstitial thermotherapy

RATIONALE AND OBJECTIVES.Laser-induced interstitial thermotherapy (LITT) may become an attractive modality for minimally invasive tumor therapy. Magnetic resonance imaging (MRI) could be used to assist this procedure. METHODS.A Tl-weighted turbo fast low-angle shot (FLASH) sequence for on-line monitoring of the laserinfluenced region (liver, muscle) was investigated. Sequence parameters were optimized for maximal image contrast. Magnetic resonance imaging-controlled LITT was performed in vitro, in vivo (rabbits), and in 8 human investigations (6 patients). Special laser applicators were used to establish a uniform laser light distribution. RESULTS.With the MRI sequence used, the LITT region is visualized as a bright area outlined by a dark border. This dark border corresponds to an isotherm of 45 ± 2 °C depending on the sequence parameters used. CONCLUSION.With the Tl-weighted turbo-FLASH sequence, MRI can be used for on-line monitoring of interstitial laserinduced thermotherapy in moving organs.

Gadolinium-ethoxybenzyl-DTPA as a hepatobiliary contrast agent for use in MR cholangiography: results of an in vivo phase-I clinical evaluation

Abstract. The purpose of this study was to investigate the time course of contrast enhancement in bile ducts and the gallbladder (GB) after injection of gadolinium-ethoxybenzyl-DTPA (Gd-EOB-DTPA). In a clinical phase-I study, MR imaging at 1.5T was performed in 16 healthy volunteers with four different doses of Gd-EOB-DTPA (10, 25, 50, and 100 μmol/kg b. w., four volunteers per dosage). The study protocol comprised a heavily T1-weighted fast multiplanar gradient-echo (GE) sequence before and at increasing intervals for up to 360 min after injection of Gd-EOB-DTPA. The signal enhancement was evaluated in extra- and intrahepatic bile ducts as well as in the GB. In all 16 volunteers the common bile duct showed intense signal enhancement beginning 5–16 min after injection (mean 10 min) and persisting for at least 120 min in 4 subjects and for 360 min in 12 subjects. The duration of signal enhancement was significantly (p < 0.05) longer for higher doses (50, 100 μmol/kg) than for lower doses (10, 25 μmol/kg). Intrahepatic bile ducts were hyperintense as compared with liver parenchyma in all subjects receiving 10 μmol/kg from approximately 50–120 min after contrast agent application. Intrahepatic bile ducts were not displayed using the higher doses, probably because of the strong enhancement of the liver parenchyma. Gallbladder contrasting was achieved in all cases beginning 7–33 min after injection (mean 19 min) and remained visible for up to 360 min in 94 %. Hyperintense visualization of normal extrahepatic bile ducts as well as the GB is regularly achieved with the hepatobiliary contrast agent Gd-EOB-DTPA. The dosage for hyperintense visualization of intrahepatic bile ducts is 10 μmol/kg.

Contrast-Enhanced Abdominal Angiographic CT for Intra-abdominal Tumor Embolization: A New Tool for Vessel and Soft Tissue Visualization

C-Arm cone-beam computed tomography (CACT), is a relatively new technique that uses data acquired with a flat-panel detector C-arm angiography system during an interventional procedure to reconstruct CT-like images. The purpose of this Technical Note is to present the technique, feasibility, and added value of CACT in five patients who underwent abdominal transarterial chemoembolization procedures. Target organs for the chemoembolizations were kidney, liver, and pancreas and a liposarcoma infiltrating the duodenum. The time for patient positioning, C-arm and system preparation, CACT raw data acquisition, and data reconstruction for a single CACT study ranged from 6 to 12 min. The volume data set produced by the workstation was interactively reformatted using maximum intensity projections and multiplanar reconstructions. As part of an angiography system CACT provided essential information on vascular anatomy, therapy endpoints, and immediate follow-up during and immediately after the abdominal interventions without patient transfer. The quality of CACT images was sufficient to influence the course of treatment. This technology has the potential to expedite any interventional procedure that requires three-dimensional information and navigation.

Iron-oxide-enhanced magnetic resonance imaging of atherosclerotic plaques: postmortem analysis of accuracy, inter-observer agreement, and pitfalls.

Schmitz SA, Taupitz M, Wagner S, et al. Iron-oxide-enhanced magnetic resonance imaging of atherosclerotic plaques: postmortem analysis of accuracy, inter-observer agreement, and pitfalls. Invest Radiol 2002;37:405–411. introduction. Contrast-enhanced magnetic resonance (MR) imaging using ultra small superparamagnetic iron oxide (USPIO) particles is a new noninvasive modality for imaging inflammatory atherosclerotic plaques. We determined the accuracy, interobserver agreement, and potential sources of error of this technique by means of postmortem MR imaging of aortic preparations. material and methods.Anesthetized atherosclerotic Watanabe heritable hyperlipidemic (WHHL) rabbits were studied after administration of different dosages of intravenous USPIO (DDM 43/34, IDF Berlin, Germany) and different postcontrast time intervals. A (n = 5) received 0 &mgr;mol Fe/kg. B (n = 5) received 50 &mgr;mol Fe/kg, 8-hour postcontrast interval. C (n = 5) received 50 &mgr;mol, 24 hours. D received 200 &mgr;mol, 48 hours. The aortas were removed and 3-mm segments prepared for postmortem examination by MR imaging using a T2-weighted gradient-echo sequence (TR/TE/FA; 41 milliseconds/11 milliseconds/15°), radiography (mammography), and histology (iron staining). USPIO accumulation was defined as the presence of 20 iron-positive cells per microscopic view (×100 magnification). Two independent readers analyzed the MR images and rated their confidence level for a positive MRI finding, defined as a focal signal loss, on a 5-point scale. The results were evaluated by receiver-operator characteristic (ROC) analysis. results. Of a total of 621 vessel segments technically acceptable for evaluation, 534 were histologically negative and 87 positive. Accuracy, expressed as the area under the ROC curve, was 0.85 for reader 1 and 0.88 for reader 2. Interobserver agreement was 0.67. False-positive findings were established by at least one reader for 121 of the 621 segments, false-negative findings for only 15 segments. Calcifications and mural thrombi were identified as potential sources of error of the method. conclusion. Postmortem USPIO-enhanced MR imaging of atherosclerotic plaques showed a high accuracy and good interobserver agreement in the animal model used here. Further optimization of the method should aim at reducing the rather high percentage of false-positive results.

MR-guided interstitial laser-induced thermotherapy of hepatic metastasis combined with arterial blood flow reduction: technique and first clinical results in an open MR system.

The feasibility and safety of percutaneous laser‐induced thermotherapy (LITT) of liver metastases in an open low‐field magnetic resonance imaging (MRI) system combined with microsphere‐modulated blood flow reduction were tested. Nd:YAG laser therapy with an internally cooled laser applicator was performed under local anesthesia on 20 patients with 34 liver metastases. To increase the effectivenes of LITT, degradable starch microspheres were injected into the proper hepatic artery through an MR‐visible catheter initially inserted under fluoroscopy. Near real‐time imaging was used for positioning the laser applicator. A T1‐weighted gradient‐echo breath‐hold sequence was used for catheter localization and temperature monitoring. The volumes of the liver metastases and the thermonecroses were determined. MRI‐guided LITT could be performed in all patients with no clinically relevant complications. Intraprocedural imaging underestimated the extent of thermonecrosis. In conclusion, percutaneous LITT of liver metastases after injection of starch microspheres is both technically feasible and safe in an open MRI system. J. Magn. Reson. Imaging 2001;13:31–36.