Patrick Wunderbaldinger

Crosslinked iron oxides (CLIO): a new platform for the development of targeted MR contrast agents.

Monodisperse iron oxide nanoparticles (MION) has long been used in MR contrast agent research and is currently used in initial clinical trials. Chemically MION consists of a superparamagnetic iron oxide core, 3-5nm in size, and a thick coating of dextran (approximately 5-10nm in size). In order to further stabilize this compound we have reacted MION with epichlorohydrin and ammonia. Epichlorohydrin is a crosslinking agent used in the manufacture of dextran particles that connects the partly “free floating” dextran chain around the iron core. Thus, the iron becomes completely caged and the new compound called CLIO (crosslinked iron oxides) chemically stable. As the amino groups of the dextran chains become functionalized and nucleophilic, they can be used for further conjugation chemistry—we have called this compound CLIO-NH2. Especially, molecules containing sulfhydryl groups (e.g.: transferrin, bombesin) can be easily conjugated to CLIO-NH2. To show the capabilities of this new platform for targeted MR contrast agents we conjugated tat-peptides (tat is known to enable fast transport into nuclei and can be used for cell loading and labeling as well as cell trafficking studies) onto the CLIO-compound by various bifunctional reagents, such as succinimydliodoacetate. As the chemical structure of CLIO-NH2 and MION are very similar, and MION is already in clinical use, we hypothesize that the biological and physical properties of these two compounds are nearly the same, and thus, any experimental data using CLIO can be applied to a clinical setting. On the other hand, we think that the biological behavior of CLIO is altered by conjugated peptides, such as tat (CLIO-tat).

Tumor microvascular changes in antiangiogenic treatment: Assessment by magnetic resonance contrast media of different molecular weights

To test magnetic resonance (MR) contrast media of different molecular weights (MWs) for their potential to characterize noninvasively microvascular changes in an experimental tumor treatment model.

Double Inversion Recovery Imaging of the Brain: Initial Experience and Comparison with Fluid Attenuated Inversion Recovery Imaging

The purpose of this study was to evaluate the diagnostic efficacy of the double inversion recovery fast spin echo (DIR-FSE) sequence for brain imaging compared to the fluid-attenuated inversion recovery (FLAIR) sequence. DIR-FSE and FLAIR-FSE sequences were obtained and compared side by side. Image assessment criteria included lesion conspicuity, contrast between different types of normal tissue, image quality, and artifacts. In addition, contrast ratios and contrast-to-noise ratios were determined. Scan time of DIR-FSE was 33% longer than scan time of FLAIR-FSE. Overall lesion conspicuity was equal on DIR-FSE and FLAIR-FSE; however, DIR-FSE showed particular advantages for infratentorial lesions and lesions with only poor contrast on T2-weighted images, whereas FLAIR was slightly superior for small superficial cerebral abnormalities. Gray-white differentiation was better with DIR-FSE. Cerebrospinal fluid suppression was equal on both sequences; cerebrospinal fluid pulsation artifacts were more pronounced on DIR-FSE but did not cause diagnostic difficulties on these images. We conclude that DIR-FSE might be obtained if infratentorial lesions and abnormalities with only slightly prolonged T2 relaxation times are suspected. Otherwise, FLAIR-FSE seems preferable.

Detection of lymph node metastases by contrast‐enhanced MRI in an experimental model

Lymph node size, the accumulation of a nodal lymphotrophic contrast agent (LCDIO), and MRI were compared as methods for detecting nodal metastases in an experimental murine model. Lymph node metastases (B16‐F1 melanoma expressing green fluorescent protein (GFP) and C57BL/6 mice) were generated to obtain a wide spectrum of nodes, including normal nodes and nodes bearing micrometastases, small metastases, or large metastases. Nodal uptake of LCDIO was measured using 111Indium‐labeled LCDIO and was found to be lower in micrometastastic nodes (4.20 ± 1.4%ID/gm) than in normal nodes (8.60 ± 0.22% ID dose/gram, P < 0.005). Nodal tumor burden was quantified from the amount of GFP present in nodes measured using the Western blot method, and was found to correlate with the decrease of LCDIO uptake. By MRI, nodes bearing small and large metastases contained regions of high signal intensity (SI) that corresponded to the visual pattern of tumor in nodes. Micrometastatic nodes were distinguishable from normal nodes based on a diffuse pattern of inhomogeneous SI. The signal‐to‐background ratio (SBR) of normal nodes (0.0112 ± 0.0061) was different from micrometastatic nodes (0.179 ± 0.080, P < 0.00046) and nodes bearing small metastases (0.723 ± 0.269, P < 0.00013), with high degrees of significance. Magn Reson Med 47:292–297, 2002.

Diagnostic Value of CT Enteroclysis Compared with Conventional Enteroclysis in Patients with Crohn's Disease

OBJECTIVE The objective of our study was to assess the diagnostic value of CT enteroclysis compared with conventional enteroclysis in patients with Crohns disease. SUBJECTS AND METHODS Fifty consecutive patients (26 women, 24 men; mean age, 36.3 years; age range, 18-52 years) with histologically proven Crohns disease underwent CT enteroclysis and conventional enteroclysis (median time interval, 21.7 days) during a symptomatic stage of their disease. Both techniques were compared with regard to diagnostic yield in assessing the presence and extent of disease. Imaging findings were compared with surgery, follow-up examinations, or both. RESULTS CT enteroclysis and conventional enteroclysis were successfully performed in all 50 patients. Crohns disease-associated radiographic changes were found in 44 patients (88%) using CT enteroclysis and in 42 patients (84%) using conventional enteroclysis. Significantly more Crohns disease-associated abnormalities were diagnosed with CT enteroclysis than with enteroclysis (p < 0.01). Minimal inflammatory changes of the mucosa were diagnosed in 44 patients (88%) using CT enteroclysis and in 42 patients (84%) using enteroclysis. Both imaging methods depicted stenotic bowel segments in 34 patients (68%), and prestenotic dilatation was diagnosed in 20 patients (40%) with CT enteroclysis and in 15 (30%) with enteroclysis. Fistulas were found in 18 patients (36%) with CT enteroclysis and in eight (16%) with enteroclysis (p < 0.01). Skip lesions could be seen in 17 (34%) and three patients (6%), respectively (p < 0.01). Conglomeration of bowel loops tumors was diagnosed with CT enteroclysis in 13 patients (26%) and in three patients (6%) using conventional enteroclysis (p < 0.01). Only CT enteroclysis depicted abscesses in eight patients (16%) (p < 0.01). CONCLUSION CT enteroclysis proved to be significantly superior to conventional enteroclysis in depicting Crohns disease-associated intra- and extramural abnormalities. CT enteroclysis is the imaging method of choice and should replace enteroclysis in patients with Crohns disease.

Findings at helical CT-enteroclysis in symptomatic patients with crohn disease: correlation with endoscopic and surgical findings.

Purpose The purpose of our study was to assess the diagnostic potential of helical CT–enteroclysis (HCTE) and to correlate our findings to endoscopic and surgical results. Methods Twenty-eight consecutive patients suffering from histologic proven Crohn disease underwent HCTE and endoscopy within 4 weeks. HCTE findings were read by two observers in consensus and compared with endoscopic and surgical results. Results Morphological signs of an acute or recurrent bowel inflammation were found in 25 of 28 (89%) patients. HCTE demonstrated accurately all mural and extramural changes of the inflamed bowel walls. Moreover, in 18 of 25 (72%) patients, HCTE depicted additional pathologic changes such as fistulas, abscesses, and skip lesions, all of which could not be visualized by endoscopy. Conclusion HCTE is an accurate technique to detect mural and extramural abnormalities in patients with Crohn disease. HCTE should be considered as a complementary imaging method to endoscopy, and should be the first imaging method especially when Crohn-associated complications are suspected.

New approaches for imaging in gene therapy.

Gene therapy is increasingly used experimentally and clinically to replace defective genes and/or impart new functions to cells and tissues. With the recent advances in vector design, improvements in transgene and prodrug activation strategies, gene therapy has been applied to a wide variety of diseases, tissues and organ systems. It is now clear that our specialty will play a critical role in gene therapy research and its clinical applications. Three aspects of gene therapy are of particular interest to imaging. The first is in delivering genes and vector products by minimally invasive interventional techniques. The second is in quantitating gene and DNA deliveries, for example, by nuclear imaging. Finally, imaging can be used to monitor the levels of transgene expression in vivo. A variety of imaging techniques including PET imaging, nuclear imaging, MR imaging and optical imaging can potentially be used to achieve the latter. This brief introductory overview is intended to summarize current strategies and illustrate the role that radiology will play in this field.

Cardiopulmonary resuscitation performed by bystanders does not increase adverse effects as assessed by chest radiography.

Important adverse effects of bystander cardiopulmonary resuscitation (CPR) are well known. We describe the number of nonmedical professional CPR-related complications in patients surviving cardiac arrest, as assessed by chest radiograph. Within 2 yr, all consecutive patients admitted to the department of emergency medicine at a university hospital who had a witnessed, nontraumatic, normothermic cardiac arrest were studied. Radiologically evaluated adverse effects were compared with Mann-Whitney U-tests between patients who received bystander basic life support (Bystander group) and patients who did not receive bystander basic life support before advanced life support was started (ALS group). For assessment of bystander CPR-associated complications, chest radiographs were used. Of 224 patients, 173 were eligible. The median age was 58 yr (interquartile range, 51–71 yr), and 126 patients (73%) were men. The incidence of adverse effects associated with assisted-ventilation maneuvers and external chest compressions did not differ significantly between groups (severe gastric insufflation, 17% vs 18% between the Bystander group [n = 59] and the ALS group [n = 96], respectively; suspicion of aspiration, 22% vs 17%, respectively; soft tissue emphysema, 2% vs 1%, respectively; and serial rib fractures, 8% vs 8%, respectively). CPR administered by nonmedical personnel did not increase the number of life support-related adverse effects in patients surviving cardiac arrest as assessed by means of chest radiograph on admission.

Pan and Sentinel Lymph Node Visualization Using a Near-Infrared Fluorescent Probe

A number of different types of agents have been employed to aid in the visualization of lymph nodes, particularly the sentinel lymph node, and to decrease the tissue destruction associated with the diagnosis of nodal metastases. The current study was performed to see if a novel macromolecular near-infrared fluorescent (NIRF) probe could be used to visualize lymph nodes after intravenous administration (pan-node visualization) or subcutaneous administration (sentinel node visualization), and serve as method for guiding dissection with interventional radiologic and surgical procedures. Cy5.5-PGC, the near-infrared dye Cy5.5 coupled to a protected graft copolymer (PGC), was injected (i.v. or s.c.) into nude mice. Twenty-four hours later white light and NIRF images were obtained on (i) the live animal, (ii) a partially dissected animal, and (iii) tissue specimens. With Cy5.5-PGC administered intravenously, axillary nodes were visualized from outside a living mouse. With partial dissection, iliac and aortic nodes were visible as concentrated foci of high-intensity NIRF signals. With subcutaneous injection in the front extremity, axillary and brachial nodes draining the injection site were easily visualized. NIRF imaging provides a nonradioactive method of visualizing lymph nodes through layers of tissue that can be employed with intravenous or subcutaneous injection.

Acute pulmonary trunk dissection in a patient with primary pulmonary hypertension

Spiral CT imaging findings including multiplanar reconstructions of an acute dissection of the pulmonary trunk in a 22-year-old female patient with primary pulmonary hypertension (PPH) are presented and discussed.