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Biomedical subjects

Thomas Beyer

Publications and source records attributed to Thomas Beyer.

29 records · Page 2Linked to original sources

Polymorphonuclear granulocytes induce antibody-dependent apoptosis in human breast cancer cells.

Recent studies in HER-2/neu-targeted immunotherapy demonstrated that polymorphonuclear neutrophils (PMN) mediated Ab-dependent cellular cytotoxicity against HER-2/neu-positive breast cancer cell lines. However, the mechanism of cell death remained unclear. We used several assays to analyze the induction of apoptosis in the breast cancer cell line SK-BR-3 via PMN-dependent Ab-dependent cellular cytotoxicity. In the presence of the HER-2/neu Ab 520C9 and PMN from healthy donors, apoptosis occurred as detected by annexin V binding and disappearance of euploid SK-BR-3 nuclei, which can be differentiated from PMN nuclei by their increased DNA contents. Apoptosis induction was observed with E:T cell ratios as low as 10:1. Laser scanning fluorescence microscopy of TUNEL tumor cells or staining for cleaved cytokeratin-18 further confirmed apoptosis of the SK-BR-3 breast cancer cells. Killing via 520C9 was dependent on the interaction with FcR on PMN, because 1) F(ab')(2) fragments of 520C9 mediated no cytotoxicity, 2) target cell death was influenced by a biallelic polymorphism of FcgammaRIIa on the effector cells, and 3) a bispecific Ab against HER-2/neu and the IgA receptor (FcalphaRI) expressed on effector cells significantly induced apoptosis. Thus, PMN induce Ab-dependent apoptosis against human breast cancer cells targeted with HER-2/neu-directed mAbs or FcR directed bispecific Abs.

Alleles↗

Non-small cell lung cancer: dual-modality PET/CT in preoperative staging.

PURPOSE: To determine the accuracy of dual-modality positron emission tomographic (PET)-computed tomographic (CT) imaging, as compared with PET alone and CT alone, in the staging of non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: Twenty-seven patients with NSCLC underwent staging with combined fluorine 18 fluorodeoxyglucose PET and CT. CT, PET, and coregistered PET/CT images were evaluated separately by two different physicians for each imaging modality, and disease stage was determined by using TNM and American Joint Committee on Cancer staging systems. Histopathologic results served as the reference standard. The statistical significance of differences among CT, PET, and PET/CT was determined by using the McNemar test. RESULTS: Overall tumor stage was correctly classified as 0-IV with CT in 19 patients, with PET in 20 patients, and with PET/CT in 26 patients. PET/CT findings when compared with PET findings led to a treatment change for four patients (15%) and when compared with CT findings led to a treatment change for five patients (19%). Differences in the accuracy of overall tumor staging between PET/CT and CT (P =.008) and between PET/CT and PET (P =.031) were significant. Primary tumor stage was correctly determined in more patients with PET/CT than with either PET alone or CT alone. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of regional lymph node staging, respectively, were 89%, 94%, 89%, 94%, and 93%, with PET/CT; 89%, 89%, 80%, 94%, and 89% with PET; and 70%, 59%, 50%, 77%, and 63% with CT. Fourteen distant metastases were detected in four patients with CT, four were detected in two patients with PET, and 17 were detected in four patients with PET/CT. CONCLUSION: Use of dual-modality PET/CT significantly increases the number of patients with correctly staged NSCLC and thus has a positive effect on treatment.

Adult↗

Dual-modality PET/CT imaging: the effect of respiratory motion on combined image quality in clinical oncology.

To reduce potential mis-registration from differences in the breathing pattern between two complementary PET and CT data sets, patients are generally allowed to breathe quietly during a dual-modality scan using a combined PET/CT tomograph. Frequently, however, local mis-registration between the CT and the PET is observed. We have evaluated the appearance, magnitude, and frequency of respiration-induced artefacts in CT images of dual-modality PET/CT studies of 62 patients. Combined PET/CT scans during normal respiration were acquired in 43 subjects using single- or dual-slice CT. Nineteen patients were scanned with a special breathing protocol (limited breath-hold technique) on a single-slice PET/CT tomograph. All subjects were injected with approximately 370 MBq of FDG, and PET/CT scanning commenced 1 h post injection. The CT images were reconstructed and, after appropriate scaling, used for on-line attenuation correction of the PET emission data. We found that respiration artefacts can occur in the majority of cases if no respiration protocol is used. When applying the limited breath-hold technique, the frequency of severe artefacts in the area of the diaphragm was reduced by half, and the spatial extent of respiration-induced artefacts was reduced by at least 40% compared with the acquisition protocols without any breathing instructions. In conclusion, special breathing protocols are effective and should be used for CT scans as part of combined imaging protocols using a dual-modality PET/CT tomograph. The results of this study can also be applied to multi-slice CT to potentially reduce further breathing artefacts in PET/CT imaging and to improve overall image quality.

Abdominal Neoplasms↗

X-ray-based attenuation correction for positron emission tomography/computed tomography scanners.

A synergy of positron emission tomography (PET)/computed tomography (CT) scanners is the use of the CT data for x-ray-based attenuation correction of the PET emission data. Current methods of measuring transmission use positron sources, gamma-ray sources, or x-ray sources. Each of the types of transmission scans involves different trade-offs of noise versus bias, with positron transmission scans having the highest noise but lowest bias, whereas x-ray scans have negligible noise but the potential for increased quantitative errors. The use of x-ray-based attenuation correction, however, has other advantages, including a lack of bias introduced from post-injection transmission scanning, which is an important practical consideration for clinical scanners, as well as reduced scan times. The sensitivity of x-ray-based attenuation correction to artifacts and quantitative errors depends on the method of translating the CT image from the effective x-ray energy of approximately 70 keV to attenuation coefficients at the PET energy of 511 keV. These translation methods are usually based on segmentation and/or scaling techniques. Errors in the PET emission image arise from positional mismatches caused by patient motion or respiration differences between the PET and CT scans; incorrect calculation of attenuation coefficients for CT contrast agents or metallic implants; or keeping the patient's arms in the field of view, which leads to truncation and/or beam-hardening (or x-ray scatter) artifacts. Proper interpretation of PET emission images corrected for attenuation by using the CT image relies on an understanding of the potential artifacts. In cases where an artifact or bias is suspected, careful inspection of all three available images (CT and PET emission with and without attenuation correction) is recommended.

Anatomy, Cross-Sectional↗

PET/CT scanners: a hardware approach to image fusion.

New technology that combines positron tomography with x-ray computed tomography (PET/CT) is available from all major vendors of PET imaging equipment: CTI, Siemens, GE, Philips. Although not all vendors have made the same design choices as those described in this review all have in common that their high performance design places a commercial CT scanner in tandem with a commercial PET scanner. The level of physical integration is actually less than that of the original prototype design where the CT and PET components were mounted on the same rotating support. There will undoubtedly be a demand for PET/CT technology with a greater level of integration, and at a reduced cost. This may be achieved through the design of a scanner specifically for combined anatomical and functional imaging, rather than a design combining separate CT and PET scanners, as in the current approaches. By avoiding the duplication of data acquisition and image reconstruction functions, for example, a more integrated design should also allow cost savings over current commercial PET/CT scanners. The goal is then to design and build a device specifically for imaging the function and anatomy of cancer in the most optimal and effective way, without conceptualizing it as combined PET and CT. The development of devices specifically for imaging a particular disease (eg, cancer) differs from the conventional approach of, for example, an all-purpose anatomical imaging device such as a CT scanner. This new concept targets more of a disease management approach rather than the usual division into the medical specialties of radiology (anatomical imaging) and nuclear medicine (functional imaging).

Equipment Design↗

Clinically feasible reconstruction of 3D whole-body PET/CT data using blurred anatomical labels.

We present the results of utilizing aligned anatomical information from CT images to locally adjust image smoothness during the reconstruction of three-dimensional (3D) whole-body positron emission tomography (PET) data. The ability of whole-body PET imaging to detect malignant neoplasms is becoming widely recognized. Potentially useful, however, is the role of whole-body PET in quantitative estimation of tracer uptake. The utility of PET in oncology is often limited by the high level of statistical noise in the images. Reduction in noise can be obtained by incorporating a priori image smoothness information from correlated anatomical information during the reconstruction of PET data. A combined PET/CT scanner allows the acquisition of accurately aligned PET and x-ray CT whole-body data. We use the Fourier rebinning algorithm (FORE) to accurately convert the 3D PET data to two-dimensional (2D) data to accelerate the image reconstruction process. The 2D datasets are reconstructed with successive over-relaxation of a penalized weighted least squares (PWLS) objective function to model the statistics of the acquisition, data corrections, and rebinning. A 3D voxel label model is presented that incorporates the anatomical information via the penalty weights of the PWLS objective function. This combination of FORE + PWLS + labels was developed as it allows for both reconstruction of 3D whole-body data sets in clinically feasible times and also the inclusion of anatomical information in such a way that convergence can be guaranteed. Since mismatches between anatomical (CT) and functional (PET) data are unavoidable in practice, the labels are 'blurred' to reflect the uncertainty associated with the anatomical information. Simulated and experimental results show the potential advantage of incorporating anatomical information by using blurred labels to calculate the penalty weights. We conclude that while the effect of this method on detection tasks is complicated and unclear, there is an improvement on the estimation task.

Computer Simulation↗

A combined PET/CT scanner: the path to true image fusion.

Software-based image fusion is used routinely for the alignment of functional and anatomical images of the brain. For other parts of the body, image registration is more problematic owing to differences in patient positioning, scanner bed profiles and the involuntary movement of internal organs. An alternative to the software approach is a scanner that acquires both function and anatomy during a single imaging session: a fusion of the technologies rather than a fusion of the images post hoc. Consequently, we designed and built a prototype combined PET and CT scanner comprising a clinical CT and a clinical PET scanner mounted together in a single gantry. Over 300 cancer patients have been imaged in the scanner to establish the clinical value of the combined PET/CT approach. The CT images were used to provide essentially noiseless attenuation correction factors for the PET data. The widespread interest created by the patient studies acquired with the prototype PET/CT stimulated commercial activity and several major vendors of medical imaging equipment now offer combined PET/CT designs. This paper reviews the development of the combined PET/CT scanner, and illustrates the clinical aspects with some typical studies in cancer patients. The potential impact on medical practice of the commercial availability of PET/CT scanner technology at affordable cost is assessed.

Aged↗

The ECAT ART Scanner for Positron Emission Tomography. 2. Research and Clinical Applications.

The ECAT ART is a low-cost positron emission tomography (PET) scanner design for which increasing interest in the use of PET, and specifically (18)FDG PET for oncological studies, has stimulated a demand. Although targeted primarily for the clinical market, the performance of the ART scanner can also meet the demands of a research environment where, in addition to [(18)F], more challenging, shorter-lived isotopes such as [(11)C], [(13)N] and [(15)O] are used. The ART has been used successfully to perform quantitative (18)FDG studies, blood flow measurements with [(15)O]water, and brain mapping studies with [(15)O]water (activation). In the clinical arena, it has been used for a wide range of applications, including epilepsy, whole-body imaging in oncology, and for cardiac viability studies. This paper explores the capability of the ECAT ART scanner to meet the demands of PET studies in both a research and clinical arena.

Journal Article↗

The ECAT ART Scanner for Positron Emission Tomography. 1. Improvements in Performance Characteristics.

The widespread use of positron emission tomography (PET) has been to some extent limited by the cost and complexity of PET instrumentation. Recognition of the wider applicability of clinical PET imaging is reflected in the ECAT ART design, a low cost PET scanner targeted for clinical applications, particularly in oncology. The ART comprises two asymmetrically opposed arrays of BGO block detectors. Each array consists of 88 (transaxial) by 24 (axial) crystals, and the arrays rotate continuously at 30 rpm to acquire a full 3D projection data set. Sensitivity and count rate limitations are key performance parameters for any imaging device. This paper reports on improved performance characteristics of the ART, achieved by operating the scanner with a decreased block integration time, reduced coincidence time window, and collimated singles transmission sources. Compared to the standard ART configuration, these modifications result in both improved count rate performance and higher quality transmission scans.

Journal Article↗

Positron emission tomography/computed tomography--imaging protocols, artifacts, and pitfalls.

There has been a longstanding interest in fused images of anatomical information, such as that provided by computed tomography (CT) or magnetic resonance imaging (MRI) systems, with biological information obtainable by positron emission tomography (PET). The near-simultaneous data acquisition in a fixed combination of a PET and a CT scanner in a combined PET/CT imaging system minimizes spatial and temporal mismatches between the modalities by eliminating the need to move the patient in between exams. In addition, using the fast CT scan for PET attenuation correction, the duration of the examination is significantly reduced compared to standalone PET imaging with standard rod-transmission sources. The main source of artifacts arises from the use of the CT-data for scatter and attenuation correction of the PET images. Today, CT reconstruction algorithms cannot account for the presence of metal implants, such as dental fillings or prostheses, properly, thus resulting in streak artifacts, which are propagated into the PET image by the attenuation correction. The transformation of attenuation coefficients at X-ray energies to those at 511 keV works well for soft tissues, bone, and air, but again is insufficient for dense CT contrast agents, such as iodine or barium. Finally, mismatches, for example, due to uncoordinated respiration result in incorrect attenuation-corrected PET images. These artifacts, however, can be minimized or avoided prospectively by careful acquisition protocol considerations. In doubt, the uncorrected images almost always allow discrimination between true and artificial finding. PET/CT has to be integrated into the diagnostic workflow for harvesting the full potential of the new modality. In particular, the diagnostic power of both, the CT and the PET within the combination must not be underestimated. By combining multiple diagnostic studies within a single examination, significant logistic advantages can be expected if the combined PET/CT examination is to replace separate state-of-the-art PET and CT exams, thus resulting in significantly accelerated diagnostics.

Humans↗