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T K Lewellen

Publications and source records attributed to T K Lewellen.

At least 19 recordsLinked to original sources
PubMed2000

A comparison of normalization effects on three whole-body cylindrical 3D PET systems.

Normalization coefficients in three-dimensional positron emission tomography (3D PET) are affected by parameters such as camera geometry and the design and arrangement of the block detectors. In this work, normalization components for three whole-body 3D-capable tomographs (the GE Advance, the Siemens/CTI962/HR+ and the Siemens/CTI951R) are compared by means of a series of scans using uniform cylindrical and rotating line sources. Where applicable, the manufacturers' normalization methods are validated, and it is shown that these methods can be improved upon by using previously published normalization protocols. Those architectural differences between the three tomographs that affect normalization are discussed with a view to drawing more general conclusions about the effect of machine architecture on normalization. The data presented suggest that uniformity of system response becomes easier to achieve as the uniformity of crystal response within the detector block is improved.

Humans↗
PubMed1999

PET imaging using dual-headed gamma cameras: an update.

Interest in clinical fluorodeoxyglucose (FDG) imaging with dual-headed gamma cameras continues to grow. In 1996, Jarritt and Acton published a review article of the use of gamma-camera systems for FDG imaging [1]. Since that article was published, considerable progress has been made in the adaptation of dual-headed camera systems for coincidence imaging. We review the basic principles of dual-headed coincidence imaging and some of the major limitations and challenges in the development of such technology. Since much of the current clinical experience with FDG imaging is based on the use of dedicated position emission tomographic (PET) systems, some comparisons of the performance limitations between dual-headed gamma-camera and dedicated PET systems are provided.

Fluorodeoxyglucose F18↗
PubMed1998

Time-of-flight PET.

Time-of-Flight (TOF) positron emission tomographs (PET) were developed during the 1980s and early 1990s. Initial investigations into the potential improvements in signal-to-noise ratios if TOF information was utilized were published in 1980. By 1982, two groups (Washington University and Commissariat á l'Energie Atomique-Laboratorie d'Electronique et de L'Informatique [CEA-LETI]) were designing and building the first TOF tomographs. A third group at the University of Texas also designed and built a TOF system. These systems were optimized for high count-rate imaging of short-lived radiotracers for applications such as cardiac blood flow. The first system put into operation for patient scans was the Super PETT I built at Washington University by Michel Ter-Pogossian and his colleagues. The Washington University group went on to design two additional versions of TOF systems and the CEA-LETI group developed two basic tomograph designs. As Bismuth Germanate (BGO)-based scanners were refined, it became clear that the TOF systems could not provide the same high spatial resolution as offered by the newer systems. The use of the fast scintillators required for TOF systems also resulted in lower intrinsic sensitivity that was only partially compensated for by the effective gain in sensitivity offered by TOF image reconstruction techniques. Further development of TOF systems was suspended in the early 1990s. With the development of new scintillators that provide more light output and are denser than those available in the 1980s and considerably faster than BGO, there is new interest in the application of TOF techniques for future tomograph designs.

Humans↗
PubMed1998

Glucose metabolism in human malignant gliomas measured quantitatively with PET, 1-[C-11]glucose and FDG: analysis of the FDG lumped constant.

UNLABELLED: Calculation of the glucose metabolic rate (MRGlc) in brain with PET and 2-[18F]fluoro-2-deoxy-D-glucose (FDG) requires knowing the rate of uptake of FDG relative to glucose from plasma into metabolite pools in the tissue. The proportionality factor for this is the FDG lumped constant (LC[FDG]), the ratio of the volumes of distribution of FDG and glucose multiplied by the hexokinase phosphorylation ratio for the two hexoses, Km(Glc) x Vm(FDG)/Km(FDG) x Vm(Glc) x MRGlc equals the FDG metabolic rate (MRFDG) divided by the LC(FDG), i.e., MRGlc = MRFDG/LC(FDG) and LC(FDG) = MRFDG/MRGlc. This investigation tested the hypothesis that LC(FDG) is significantly higher in gliomas than it is in brain uninvolved with tumor. METHODS: We imaged 40 patients with malignant gliomas with 1-[11C]glucose followed by FDG. The metabolic rates MRGlc and MRFDG were estimated for glioma and contralateral brain regions of interest by an optimization program based on three-compartment, four-rate constant models for the two hexoses. RESULTS: The LC(FDG), estimated as MRFDG/MRGlc, in gliomas was 1.40 +/- 0.46 (mean +/- s.d.; range = 0.72-3.10), whereas in non-tumor-bearing contralateral brain, it was 0.86 +/- 0.14 (range = 0.61-1.21) (p < 0.001, glioma versus contralateral brain). CONCLUSION: These data strongly suggest that the glioma LC(FDG) exceeds that of contralateral brain, that quantitation of the glioma MRGlc with FDG requires knowing the LC(FDG) specific for the glioma and that the LC(FDG) of normal brain is higher than previously reported estimates of about 0.50. 2-Fluoro-2-deoxy-D-glucose/PET studies in which glioma glucose metabolism is calculated by the autoradiographic approach with normal brain rate constants and LC(FDG) will overestimate glioma MRGlc, to the extent that the glioma LC(FDG) exceeds the normal brain LC(FDG). "Hot spots" visualized in FDG/PET studies of gliomas represent regions where MRGlc, LC(FDG) or their product is higher in glioma than it is in uninvolved brain tissue.

Autoradiography↗
PubMed1998

Carbon-11-thymidine and FDG to measure therapy response.

UNLABELLED: This study was performed to determine if PET imaging with 11C-thymidine could measure tumor response to chemotherapy early after the initiation of treatment. Imaging of deoxyriboneucleic acid biosynthesis, quantitated with 11C-thymidine, was compared with measurements of tumor energetics, obtained by imaging with 18F-fluorodeoxyglucose (FDG). METHODS: We imaged four patients with small cell lung cancer and two with high-grade sarcoma both before and approximately 1 wk after the start of chemotherapy. Thymidine and FDG studies were done on the same day. Tumor uptake was quantified by standardized uptake values (SUVs) for both tracers by the metabolic rate of FDG and thymidine flux constant (K(TdR)) using regions of interest placed on the most active part of the tumor. RESULTS: In the four patients with clinical response to treatment, both thymidine and FDG uptake markedly declined 1 wk after therapy. Thymidine measurements of SUV and K(TdR) declined by 64% +/- 15% and 84% +/- 33%, respectively. FDG SUV and the metabolic rate of FDG declined by 51% +/- 9% and 63% +/- 23%, respectively. In the patient with metastatic small cell lung cancer who had disease progression, the thymidine SUV decreased by only 8% (FDG not done). In a patient with abdominal sarcoma and progressive disease, thymidine SUV was essentially unchanged (declined by 3%), whereas FDG SUV increased by 69%. CONCLUSION: Images show a decline in both cellular energetics and proliferative rate after successful chemotherapy. In the two patients with progressive disease, thymidine uptake was unchanged 1 wk after therapy. In our limited series, K(TdR) measurements showed a complete shutdown in tumor proliferation in patients in whom FDG showed a more limited decrease in glucose metabolism.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1996

Quantifying regional hypoxia in human tumors with positron emission tomography of [18F]fluoromisonidazole: a pretherapy study of 37 patients.

PURPOSE: To assess pretreatment hypoxia in a variety of tumors using positron emission tomography (PET) after injection of the hypoxia-binding radiopharmaceutical [18F]fluoromisonidazole ([18F]FMISO). METHODS AND MATERIALS: Tumor fractional hypoxic volume (FHV) was determined in 21 nonsmall cell lung cancer patients, 7 head and neck cancer patients, 4 prostate cancer patients, and 5 patients with other malignancies by quantitative PET imaging after injection of [18F]FMISO (0.1 mCi/kg). The FHV was defined as the proportion of pixels in the imaged tumor volume with a tissue:blood [18F] activity ratio > or = 1.4 at 120-160 min postinjection. A FHV > 0 was taken as evidence for tumor hypoxia. RESULTS: Hypoxia was observed in 36 of 37 tumors studied with FMISO PET imaging; FHVs ranged from 0 to 94.7%. In nonsmall cell lung cancers (n = 21), the median FHV was 47.6% and the range, 1.3 to 94.7%. There was no correlation between tumor size and FHV. In the seven head and neck carcinomas, the median FHV was 8.8%, with a range from 0.2 to 18.9%. In the group of four prostate cancers, the median and range were 18.2% and 0 to 93.9%, while in a group of five tumors of different types the median FHV was 55.2% (range: 21.4 to 85.8%). CONCLUSIONS: Hypoxia was present in 97% of the tumors studied and the extent of hypoxia varied markedly between tumors in the same site or of the same histology. Hypoxia also was distributed heterogeneously between regions within a single tumor. These results are consistent with O2 electrode measures with other types of human tumors. The intra- and intertumor variability indicate the importance of making oxygenation measures in individual tumors and the necessity to sample as much of the tumor volume as possible.

Carcinoma, Non-Small-Cell Lung↗
PubMed1996

Scatter and attenuation correction for 111In based on energy spectrum fitting.

A combined scatter and attenuation correction that does not require a transmission scan is proposed for 111In imaging. Estimates of the unscattered intensity at both 171 and 245 keV are obtained by fitting the observed energy spectrum at each pixel or region of interest using the measured scatter-free spectrum and a simple model for scatter. The scatter model for the 171 keV peak accounts for scatter contributed by both the 171 and 245 keV emissions. After correcting for scatter, the attenuation is estimated from the observed ratio of photopeak intensities using the known difference in attenuation at the two emission energies and a model based on a point source in water. Accurate scatter correction is a prerequisite for the success of this method because scatter from the higher energy emission will otherwise contaminate the lower photopeak. This differential attenuation method (DAM) of estimating attenuation is demonstrated and calibrated using a series of point source measurements with a wedge-shaped attenuator. The observed absolute and differential attenuation are in good agreement with the narrow-beam linear attenuation coefficients for water. Estimates of precision suggest a depth resolution of 1.0-2.5 cm for realistic count densities over the clinically relevant depth range (0-25 cm). The accuracy of DAM in a more realistic attenuation environment is assessed using a hot sphere inside the anthropomorphic data spectrum torso phantom viewed from several angles (with differing attenuation). Finally, the potential of DAM for SPECT attenuation correction was investigated by computer simulation using the SIMSET Monte Carlo software. Preliminary results based on measured planar data and simulated SPECT data indicate that DAM can improve the quality and quantitative accuracy of 111In images. In one SPECT simulation study, the average error in tumor to soft-tissue ratios was reduced from 32% for uncorrected data to 8% for data corrected with DAM. However, the technique is susceptible to significant noise amplification and can cause substantial streak artifacts in low-count SPECT studies if sufficient smoothing of the depth estimates is not performed.

Biophysical Phenomena↗
PubMed1996

Energy-based scatter corrections for scintillation camera images of iodine-131.

UNLABELLED: The use of high-dose 131I antibody therapy requires accurate measurement of normal tissue uptake to optimize the therapeutic dose. One of the factors limiting the accuracy of such measurements is scatter and collimator septal penetration. This study evaluated two classes of energy-based scatter corrections for quantitative 131I imaging: window-based and spectrum-fitting. METHODS: The window-based approaches estimate scatter from data in two or three energy windows placed on either side of the 364-keV photopeak using empirical weighting factors. A set of images from spheres in an elliptical phantom were used to evaluate each of the window-based corrections. The spectrum-fitting technique estimates detected scatter at each pixel by fitting the observed energy spectrum with a function that models the photopeak and scatter, and which incorporates the response function of the camera. This technique was evaluated using a set of Rollo phantom images. RESULTS: All of the window-based methods performed significantly better than a single photopeak window (338-389 keV), but the weighting factors were found to depend on the object being imaged. For images contaminated with scatter, the spectrum-fitting method significantly improved quantitation over photopeak windowing. Little difference, however, between any of the methods was observed for images containing small amounts of scatter. CONCLUSION: Most clinical 131I imaging protocols will benefit from qualitative and quantitative improvements provided by the spectrum-fitting scatter correction. The technique offers the practical advantage that it does not require phantom-based calibrations. Finally, our results suggest that septal penetration and scatter in the collimator and other detector-head components are important sources of error in quantitative 131I images.

Gamma Cameras↗
PubMed1995

Evaluation of oxygenation status during fractionated radiotherapy in human nonsmall cell lung cancers using [F-18]fluoromisonidazole positron emission tomography.

PURPOSE: Recent clinical investigations have shown a strong correlation between pretreatment tumor hypoxia and poor response to radiotherapy. These observations raise questions about standard assumptions of tumor reoxygenation during radiotherapy, which has been poorly studied in human cancers. Positron emission tomography (PET) imaging of [F-18]fluoromisonidazole (FMISO) uptake allows noninvasive assessment of tumor hypoxia, and is amenable for repeated studies during fractionated radiotherapy to systematically evaluate changes in tumor oxygenation. METHODS AND MATERIALS: Seven patients with locally advanced nonsmall cell lung cancers underwent sequential [F-18]FMISO PET imaging while receiving primary radiotherapy. Computed tomograms were used to calculate tumor volumes, define tumor extent for PET image analysis, and assist in PET image registration between serial studies. Fractional hypoxic volume (FHV) was calculated for each study as the percentage of pixels within the analyzed imaged tumor volume with a tumor:blood [F-18]FMISO ratio > or = 1.4 by 120 min after injection. Serial FHVs were compared for each patient. RESULTS: Pretreatment FHVs ranged from 20-84% (median 58%). Subsequent FHVs varied from 8-79% (median 29%) at midtreatment, and ranged from 3-65% (median 22%) by the end of radiotherapy. One patient had essentially no detectable residual tumor hypoxia by the end of radiation, while two others showed no apparent decrease in serial FHVs. There was no correlation between tumor size and pretreatment FHV. CONCLUSIONS: Although there is a general tendency toward improved oxygenation in human tumors during fractionated radiotherapy, these changes are unpredictable and may be insufficient in extent and timing to overcome the negative effects of existing pretreatment hypoxia. Selection of patients for clinical trials addressing radioresistant hypoxic cancers can be appropriately achieved through single pretreatment evaluations of tumor hypoxia.

Aged↗
PubMed1995

Multiwindow scatter correction techniques in single-photon imaging.

We studied the performance of linear scatter correction methods for single-photon imaging with Tc-99m and Tl-201, using a numerical model of the Rollo phantom and measurements with a gamma camera modified to record position and energy information in list mode form. We compared the performance of these methods to per-image optimized linear methods and to locally adaptive linear methods, and developed estimates of the limits on accuracy of scatter correction imposed by the presence of Poisson noise. For both Tc-99m and Tl-201 imaging at a fixed depth, particularly at low count rates, the performance of dual-window methods, or of adaptive methods, is near the best possible for linear methods. Smoothing of the scatter estimate results in minor improvement for Tl-201. Substantial gaps between the performance of any of these linear methods and the limits imposed by Poisson noise remain and are due primarily to bias, with the gap for Tl-201 being larger than that for Tc-99m.

Algorithms↗
PubMed1994

Post therapy imaging in high dose I-131 radioimmunotherapy patients.

The biodistribution of a trace-labeled I-131 antibody is used to predict the biodistribution of a high dose I-131 antibody for therapy. Internal radiation dose estimates derived from the trace-labeled antibody have been used to determine the I-131 doses in a phase I escalating dose therapy trial for hematologic malignancy. To confirm the hypothesis that the distribution of a trace- and high-dose labeled antibodies are similar, both trace (7-11 mCi, 259-407 MBq) and high-dose (100-800 mCi, 3700-29600 MBq) I-131 radiolabeled antibody infusion were imaged in 12 patients who were treated for leukemia or lymphoma. With specialized imaging techniques using lead attenuation sheets, clearance data from organs were obtained from serial gamma camera images. Biological clearance half times of I-131 from both trace and therapy level doses were in agreement. An exception was a patient who developed human antimouse antibody before therapy, and subsequently had rapid clearance of the therapy dose. The method was feasible, yielded reproducible results, and provided critical data for relating therapy toxicity to radiation absorbed dose estimates.

Biophysical Phenomena↗
PubMed1992

Imaging of hypoxia in human tumors with [F-18]fluoromisonidazole.

Fluoromisonidazole (FMISO) has been shown to bind selectively to hypoxic cells in vitro and in vivo at radiobiologically significant oxygen levels. When labeled with the positron emitter fluorine-18 (F-18), its uptake in tissue can be detected quantitatively with high precision by positron emission transaxial tomography (PETT). This paper presents the first experiences with PETT imaging of [F-18]FMISO uptake in human malignancies, and describes the development of this technique as a tool for the non-invasive assessment of tumor hypoxia. Eight patients with selected cancers were imaged prior to primary radiotherapy, and 3 returned for follow-up scans, for a total of 11 imaging studies. Six of eight pre-radiotherapy studies revealed retention of [F-18]FMISO in tumors that significantly exceeded plasma concentrations by 2 hr after drug injection; all five patients with head and neck primaries had such "positive" scans. An analytic method for the interpretation of [F-18] FMISO PETT images is presented, defining hypoxic elements within a tumor volume as regions with a threshold regional tumor:plasma [F-18]FMISO ratio of greater than or equal to 1.4 by 2 or more hours after injection. Toward the end of a course of fractionated radiotherapy, three repeat studies in patients with initially positive scans showed no tumor accumulation of drug above the threshold ratio of 1.4, suggesting reoxygenation had occurred. Pharmacokinetic and dosimetry data support continued use of [F-18]FMISO as a safe hypoxia probe. Two imaging protocols have been developed for human studies; a long protocol allows for more complete biodistribution and dosimetry information, and a shorter protocol facilitates increased patient accrual by applying a simple, clinically expedient imaging procedure. When correlated with tumor outcome, [F-18]FMISO PETT imaging may be developed as a predictor of tumor response to conventional radiotherapy. The implications of this technique in addressing persistent questions of tumor hypoxia in human oncology is discussed.

Cell Hypoxia↗
PubMed1992

Noninvasive detection of hypoxic myocardium using fluorine-18-fluoromisonidazole and positron emission tomography.

Fluoromisonidazole (FMISO) is metabolically trapped in viable cells as a function of reduced cellular pO2. Therefore [18F]-FMISO is potentially useful for evaluating patients with hypoxic but viable myocardium. The goal of this study was to investigate [18F]FMISO uptake in ischemic myocardium non-invasively using positron emission tomography (PET). Studies were performed in 10 open-chest dogs subjected to either complete (Group 1, n = 5) or partial (Group 2, n = 5) occlusion of the left anterior descending coronary artery. The tracer was administered by intravenous bolus following the onset of ischemia and serial PET images were acquired for the next 4 hr. In Group 1, viability was assessed using histochemical staining (nitroblue tetrazolium, NBT) and 99mTc-pyrophosphate (Tc-PYP). In Group 2, viability was assessed using measurements of regional wall motion, histochemical staining and histology (two animals). In each study, PET images obtained at times between 2 and 4 hr postinjection showed specific enhancement of tracer activity in the distal anterior wall and apex of the left ventricle. At 4 hr, the tissue-to-blood pool count ratio was significantly higher in ischemic regions; 1.8 +/- 0.4 for Group 1 and 1.6 +/- 0.2 for Group 2 versus 1.0 +/- 0.1 in nonischemic regions. Postmortem tissue sampling of Group 1 hearts showed significant FMISO retention in samples without evidence for infarction, either by NBT or Tc-PYP deposition, as well as in more severely ischemic regions. In Group 2 animals, FMISO was retained in myocardial regions with reduced blood flow (microspheres), which exhibited improved contraction following reperfusion. We conclude that PET imaging of [18F]FMISO is a promising technique for the noninvasive identification of viable hypoxic myocardium.

Animals↗
PubMed1992

A method for imaging therapeutic doses of iodine-131 with a clinical gamma camera.

Imaging therapeutic doses of 131I-labeled monoclonal antibody would provide valuable biodistribution data for dosimetry, but gamma cameras are unable to accurately handle the corresponding high counting rate. To image patients undergoing radioimmunotherapy, we attached 1.6- to 6.4-mm-thick Pb sheets to the front face of a high-energy parallel-hole collimator. With this method, we were able to acquire planar images of up to 700 mCi of radiolabeled antibody 1 hr after infusion. Monte Carlo simulations indicated that less than 7% of the events counted in the photopeak window were due to 364-keV photons that scattered in the Pb attenuator. Measurements indicated that the Pb sheets degraded system resolution by no more than 13%. A quantitative comparison of trace and therapy biodistribution data from planar images of the same patient was made using corrections for Pb sheet attenuation and camera deadtime.

Gamma Cameras↗
PubMed1991

Performance standards in positron emission tomography.

A standard set of performance measurements is proposed for use with positron emission tomographs. This set of measurements has been developed jointly by the Computer and Instrumentation Council of the Society of Nuclear Medicine and the National Electrical Manufacturers Association. The measurements include tests of spatial resolution, scatter fraction, sensitivity, count rate losses and randoms, uniformity, scatter correction, attenuation correction, and count rate linearity correction.

Humans↗
PubMed1989

Evaluation of a clinical scintillation camera with pulse tail extrapolation electronics.

The performance of a new scintillation camera, designed for high event rate capability, was evaluated. The system consisted of a 400 mm field-of-view Nal(T1) camera with 61 photomultiplier tubes and modified General Electric Starport electronics. A significant feature of the system was circuitry for performing pulse tail extrapolation and separation of individual pulses involved in pulse pile-up events. System deadtime, flood field uniformity, energy resolution, linearity, spatial resolution, and bar phantom image quality were evaluated for count rates up to 200 kcps in a 20% photopeak window. Our results indicate that this camera design does not compromise image quality at normal clinical count rates and at higher event rates can provide better image quality and increased sensitivity over many Anger cameras currently employed in nuclear medicine.

Evaluation Studies as Topic↗