Biomedical subjects
Publications and source records attributed to Patrick Wunderbaldinger.
Optical imaging or near infrared fluorescence (NIRF) imaging using enzymatically activatable smart probes is an exiting new imaging modality that can also be used for lymph node visualization and detection. This review intends to briefly summarize general aspects of optical imaging and its capabilities for lymph node imaging.
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OBJECTIVE: The objective of our study was to assess the diagnostic value of CT enteroclysis compared with conventional enteroclysis in patients with Crohn's disease. SUBJECTS AND METHODS: Fifty consecutive patients (26 women, 24 men; mean age, 36.3 years; age range, 18-52 years) with histologically proven Crohn's 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. Crohn's disease-associated radiographic changes were found in 44 patients (88%) using CT enteroclysis and in 42 patients (84%) using conventional enteroclysis. Significantly more Crohn's 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 Crohn's disease-associated intra- and extramural abnormalities. CT enteroclysis is the imaging method of choice and should replace enteroclysis in patients with Crohn's disease.
PURPOSE: 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. MATERIALS AND METHODS: MD-MBA-435, a poorly differentiated human breast cancer cell line, was implanted into 31 female homozygous athymic rats. Animals were assigned randomly to a control (saline) or drug treatment (monoclonal antibody vascular endothelial growth factor (Mab-VEGF) antibody) group. In both groups, dynamic MR imaging (MRI) was performed in each animal using up to three different contrast media on sequential days at baseline and follow-up examination. The MWs of the contrast media used ranged from 557 Da to 92 kDa. Using a bidirectional kinetic model, tumor microvessel characteristics, including the fractional plasma volume (fPV) and transendothelial permeability (K(PS)), were estimated for each contrast medium. These microvascular characteristics were compared between drug and control groups and between contrast media of different MWs. RESULTS: Tumors grew significantly slower (P < 0.0005) in the drug treatment group than in the control group. Mean K(PS) and fPV values decreased significantly (P < 0.05) in the Mab-VEGF antibody-treated group compared to baseline values using intermediate or macromolecular contrast media (MMCM), but did not change significantly using small molecular contrast media (SMCM). In the control groups, mean K(PS) and mean fPV values did not reach statistical significance for any of the contrast media used. CONCLUSION: Therapeutic effects of a Mab-VEGF antibody on tumor microvessel characteristics can be monitored by dynamic MRI. Intermediate-size agents, such as Gadomer-17, offer a substantial dynamic range and are less limited by imaging precision and therefore should be considered a practical alternative to monitor antiangiogenesis treatment effects in a clinical setting.
UNLABELLED: Nuclear medicine plays an important role in the imaging of neuroendocrine tumors (NETs). Somatostatin receptor scintigraphy (SRS) with (111)In-labeled somatostatin receptor analogs is a standard procedure for the detection and staging of NET. Based on the ability of NETs to store biogenic amines, this study evaluated whether 6-(18)F-fluoro-L-DOPA ((18)F-FDOPA) is a suitable PET tracer for NETs. METHODS: Twenty-three patients with histologically verified NETs in advanced stages were consecutively enrolled in the study. All patients underwent PET with (18)F-FDOPA, CT, and SRS within 6 wk. In patients with discrepancies between nuclear medicine and radiologic methods, follow-up investigations were performed by CT, MRI, and ultrasound. (18)F-FDOPA PET with attenuation correction was done 30 and 90 min after injection from the neck to the upper legs. SRS was performed with (111)In-DOTA-D-Phe(1)-Tyr(3)-octreotide at 6 and 24 h. All images were read without knowledge of the results of the other modalities. In every patient, the following regions were evaluated separately: bones, mediastinum, lungs, liver, pancreas, and others, including the abdominal and supraclavicular lymph nodes, spleen, and soft- tissue lesions. The findings were confirmed by clinical examination. The nuclear medicine methods were compared against morphologic imaging, which was considered as gold standard. RESULTS: The most frequently involved organs or regions were the liver (prevalence, 70%) and bone (52%), followed by mediastinal foci (31%), the lungs (22%), and the pancreas (13%). Fifty-two percent of patients had various lymphatic lesions. (18)F-FDOPA was most accurate in detecting skeletal lesions (sensitivity, 100%; specificity, 91%) but was insufficient in the lung (sensitivity, 20%; specificity, 94%); SRS yielded its best results in the liver (sensitivity, 75%; specificity, 100%); however, it was less accurate than PET in all organs. In about 40%, initial CT failed to detect bone metastases shown by PET that were later on verified by radiologic follow-up. CONCLUSION: (18)F-FDOPA PET performs better than SRS in visualizing NETs and may even do better than CT for bone lesions. SRS is essential to establish the usefulness of therapy with somatostatin analogs, yet is less accurate than (18)F-FDOPA PET for staging.
Imaging of amino acid transport in brain tumours is more sensitive than fluorine-18 2-fluoro-deoxyglucose positron emission tomography (PET). The most frequently used tracer in this field is carbon-11 methionine (MET), which is unavailable for PET centres without a cyclotron because of its short half-life. The purpose of this study was to evaluate the performance of 3,4-dihydroxy-6-[(18)F]fluoro-phenylalanine (FDOPA) in this setting, in comparison with MET. Twenty patients with known supratentorial brain lesions were referred for PET scans with FDOPA and MET. The diagnoses were 18 primary brain tumours, one metastasis and one non-neoplastic cerebral lesion. All 20 patients underwent PET with FDOPA (100 MBq, 20 min p.i.), and 19 of them also had PET scans with MET (800 MBq, 20 min p.i.). In all but one patient a histological diagnosis was available. In 15 subjects, histology was known from previous surgical interventions; in five of these patients, as well as in four previously untreated patients, histology was obtained after PET. In one untreated patient, confirmation of PET was possible solely by correlation with MRI; a histological diagnosis became available 10 months later. MET and FDOPA images matched in all patients and showed all lesions as hot spots with higher uptake than in the contralateral brain. Standardised uptake value ratios, tumour/contralateral side (mean+/-SD), were 2.05+/-0.91 for MET and 2.04+/-0.53 for FDOPA (NS). The benign lesion, which biopsy revealed to be a focal demyelination, was false positive, showing increased uptake of MET and FDOPA. We conclude that FDOPA is accurate as a surrogate for MET in imaging amino acid transport in malignant cerebral lesions for the purpose of visualisation of vital tumour tissue. It combines the good physical properties of (18)F with the pharmacological properties of MET and might therefore be a valuable PET radiopharmaceutical in brain tumour imaging.
The aim of this study was to validate the use of near infrared fluorescence imaging (NIRF) using enzyme-sensitive optical probes for lymph node detection. An optical contrast probe that is activated by cystein proteases, such as cathepsin B, was used to visualize lymph nodes by NIRF reflectance imaging. In order to quantitate the uptake of the optical probe in lymphatic tissue, the biodistribution was assessed using the Indium-111 labeled optical probe. Sixteen Balb-c mice were injected either intravenously (i.v.) or subcutaneously (s.c.) with the NIRF-probe (2 micromol cyanine (Cy)/animal; i.v., n=10; s.c., n=6) and imaged 24 h after injection. Signal intensities and target-to-background ratios of various lymph nodes were measured by manual regions of interest (ROIs). Additional signal intensity measurements were performed of excised lymph nodes (n=21) from i.v. injected mice (24 h after injection) and compared with excised lymph nodes (n=8) of non-injected mice. The probe employed in this study was lymphotropic with approximately 3-4% accumulation in lymph nodes (3.4+/-0.8% ID/g). Measurements of the excised lymph nodes (after i.v. injection) confirmed a significant increase in lymph node fluorescence signal from baseline 26+/-7.6 arbitary units (AU) to 146+/-10.9 AU (p<0.0001). A significant increase in lymph node fluorescence signal was also seen in vivo throughout the body after i.v. injection (96+/-7.8 AU) and/or regionally after s.c. injection (141+/-11.5 AU) in comparison with baseline autofluorescence (26+/-7.6 AU). Target-to-background ratio was significantly higher after s.c. injection (6.6%+/-0.81) compared with i.v. injection (4.8+/-0.67%). Detection and visualization of lymph nodes is feasible by NIRF imaging using a cystein-protease sensitive optical 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.
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 (111)Indium-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.
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OBJECTIVE: The aim of this study was to illustrate and discuss the sonographic spectrum of surgically proven cystic nodal metastases from papillary thyroid carcinoma. By correlative evaluation of the sonographic imaging findings to gross pathology and histology, our purpose was to provide useful hints to differentiate cystic lymph node metastases from other benign cystic neck lesions such as branchial cysts. MATERIALS AND METHODS: Sonographic examinations of 74 patients (47 women, 27 men; mean age, 49 years) with 97 histologically confirmed cystic lymph nodes metastases from papillary thyroid carcinoma were included in the study. The anatomic relationship of the nodes relative to the primary tumor was recorded, and all cystic nodes were qualitatively categorized as either simple (purely cystic) or complex (thickened outer wall, internal nodules, internal septations, and calcifications). All imaging findings were compared with gross pathologic specimens. RESULTS: Most of the cystic metastases were ipsilateral to the primary tumor (87.8%) and located in the mid or lower jugular chain (73.2%). In 14.9% of all patients, cystic lymph node metastases were the initial manifestation of disease. Only 6.2% of all lymph node metastases were purely cystic (all of these occurred in patients less than 35 years old). Of the 91 complex metastases, a thickened outer wall was present in 35.2% of patients, internal nodules in 42.9%, and internal septations in 57.1%. No calcifications were seen in the 91 complex metastases, and two or more findings were seen in 23.1%. All sonographic findings were verified by surgery. CONCLUSION: In most of the patients, cystic lymph node metastases are characterized sonographically by the presence of a thickened outer wall, internal echoes, internal nodularity, and septations. However, in younger patients, the lymph nodes might appear purely cystic, thereby mimicking branchial cysts and thus requiring biopsy for final diagnosis and therapy planning.
OBJECTIVE: Our purpose was to compare the two different body positions for stereotactic large-core breast biopsy with regard to sensitivity, specificity, and accuracy, as well as complication rate. SUBJECTS AND METHODS: Two hundred patients had large-core breast biopsy performed either in the prone (n = 100) or in the sitting (n = 100) position and subsequently underwent surgical resection. The histopathologic findings of large-core breast biopsy and surgery of all 200 patients were compared; sensitivity, specificity, and accuracy were calculated for both groups. Biopsy-associated complications were prospectively recorded for immediate and delayed events and for technical failures in both groups. RESULTS: Sensitivity (96%), specificity (100%), and accuracy (98%) were the same for both groups with two false-negative findings in each group. The two false-negative results in the sitting group were caused by vasovagal reactions, whereas those in the prone group were caused by technical failure and uncomfortable biopsy position. More statistically significant complications (seven vs four, p < 0.001) and vasovagal reactions (seven vs two, p < 0.0001) were seen in the sitting group. CONCLUSION: For performance of large-core breast biopsy, both the prone and sitting positions are reliable and accurate methods. However, vasovagal reactions that could potentially complicate biopsy were seen significantly more often in the sitting position.
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Superparamagnetic nanoparticles have a number of important biomedical applications, serving as MR contrast agents for imaging specific molecular targets, as reagents for cell labeling and cell tracking, and for the isolation of specific classes of cells. We have determined the physical and biological properties of MION-47 and amino-CLIO, nanoparticles which serve as precursors for the synthesis of targeted MR contrast agents, and Tat-CLIO, a nanoparticle used as a cell labeling reagent. Blood half-lives for MION-47 and amino-CLIO were 682 +/- 34 and 655 +/- 37 min, respectively. The attachment of 9.7 tat peptides per crystal to amino-CLIO resulted in a reduction in blood half-life to 47 +/- 6 min. MION-47, amino-CLIO, and Tat-CLIO were present in highest concentrations in liver and spleen and lymph nodes, where concentrations for all three nanoparticles ranged from 8.80 to 6.11% of injected dose per gram. Twenty-four hours after the intravenous injection of amino-CLIO, the nanoparticle was concentrated in cells surrounding hepatic blood vessels (endothelial and Kupffer cells), in a fashion similar to that obtained with other nanoparticle preparations. In contrast, Tat-CLIO was present as numerous discrete foci of intense fluorescence throughout the parenchyma. Using the peptide as a component of future nanoparticles, it might be possible to design sensors for the detection of macromolecules present in intracellular compartments.
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.