Joseph A Thie

University of Tennessee, Knoxville, Tennessee, United States

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Publications (36)85.58 Total impact

  • Joseph A Thie
    Journal of Nuclear Medicine 12/2013; · 5.77 Impact Factor
  • Joseph A Thie
    Journal of Nuclear Medicine 10/2012; · 5.77 Impact Factor
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    Joseph A Thie
    Journal of Nuclear Medicine 06/2010; 51(6):998-9. · 5.77 Impact Factor
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    ABSTRACT: The objective of this retrospective study was to assess the likelihood of extrahepatic metastases based on tumor metabolic load index (TMLI) for patients with colorectal liver metastases to determine the potential intermediate endpoint of yttrium-90 (Y-90) microsphere liver-directed therapy. Forty-eight (48) patients with colorectal metastatic cancer of the liver who were referred for Y-90 microsphere therapy and F-18 fluoro-2-deoxy-D-glucose positron emission tomography (PET) imaging were included. All patients had baseline computed tomography, hepatic angiography, and planning intra-arterial technetium-99m macro-aggregated albumin scans. Pretreatment PET images were analyzed by visual inspection of extrahepatic metastases and by computer quantification of total liver tumor metabolism. For each patient, regions of interest were drawn along the liver edge to measure total liver standard uptake value on axial images, covering the entire span of the liver. The total liver standard uptake value was then converted by logarithm in equivalent volumes of liver mass to obtain TMLI for comparison. A Levene test for equality of variances and t-tests were used for comparing pretreatment TMLIs of patients with or without extrahepatic metastasis. Discriminant and receiver operating characteristic (ROC) analyses were used to obtain a cutoff value with highest specificity in predicting negative extrahepatic metastasis. There were 21 and 27 patients identified as negative and positive for extrahepatic metastasis, respectively. The TMLI of the group with negative extrahepatic metastasis was significantly lower than that with positive extrahepatic metastasis (10.22 + 0.32 versus 10.74 + 0.57, p < 0.0005). The cutoff TMLI with 100% specificity was found to be 10.65. There was a significant difference in liver tumor load with respect to the presence or absence of an extrahepatic metastatic tumor as evaluated objectively with PET. This leads to the identification of TMLI threshold, below which extrahepatic metastases are unlikely and thus may provide guidance for Y-90 therapy.
    Cancer Biotherapy & Radiopharmaceuticals 04/2010; 25(2):233-6. · 1.44 Impact Factor
  • Joseph A Thie
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    ABSTRACT: The intention here is to enhance the usefulness of the Gjedde-Patlak plot of dynamic positron emission tomography (PET) tracer uptake. Two additional parameters closely related to the physiologically significant and diagnostically useful phosphorylation rate k (3) are therefore studied. Additionally, their inter-institutional transportability is examined. The two traditional parameters obtained from a Patlak plot are its slope Ki and its usually ignored tissue/plasma (=Q/Cp) axis intercept V. As a useful result, a normalized uptake rate may be defined as k=Ki /V. This is can be theoretically close to k (3). Similar to this an alternative normalized uptake rate is defined as k (3)' =Ki /V '. Here, V ' would be a composite of model rate constants, reasonably known a priori, and the measured V so as to depend less on errors in the latter. Parameter determination demonstrations utilize data from the 2-deoxy-2-[F-18]fluoro-D-glucose(FDG)-PET literature. Using median k (i) values from 24 FDG dynamic studies and algebraic relationships, on average: k=1.07 k (3)(r=0.97), and k (3)' =0.95k (3) (r=0.91). A skeletal muscle case also demonstrates agreements with k (3). For liver malignancies k and k (3)' can be diagnostically slightly superior to Ki. Unaffected by institutionally dependent Q and Cp calibrations and methods, these can be more robust than Ki in a number of circumstances. Two studied physiologically meaningful parameters, close to the diagnostically important k (3), can supplement Ki and enhance Patlak analysis by appropriately utilizing normally ignored information. Hitherto, k (3) was obtainable only by complex nonlinear least squares compartmental model analysis. The additional parameters can have more robust inter-institutional transportability than Ki.
    Molecular imaging and biology: MIB: the official publication of the Academy of Molecular Imaging 12/2009; 12(5):479-87. · 2.47 Impact Factor
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    ABSTRACT: Known errors in the standardized uptake value (SUV) caused by variations in subject weights W encountered can be corrected by lean body mass or body surface area (bsa) algorithms replacing W in calculations. However this is infrequently done. The aims of the work here are: quantify sensitivity to W, encourage SUV correction with an approach minimally differing from tradition, and show what improvements in the SUV coefficient of variation (cv) for a population can be expected. Selected for analyses were 2-deoxy-2-[F-18]fluoro-D-glucose (FDG) SUV data from positron emission tomography (PET) and PET/computed tomography (CT) scans at the University of Tennessee as well as from the literature. A weight sensitivity index was defined as -n=slope of ln(SUV/W) vs. lnW. The portion of the SUV variability due to this trend is removed by using the defined [formula: see text], or a virtually equal SUVm using [formula: see text], with Q and ID being tissue specific-activity and injected dose. [formula: see text] measures performance. Adapting to animal studies' tradition, [formula: see text] is preferred over the conventional [formula: see text]. For FDG in adults [formula: see text] from averaging over most tissues. In children, however, [formula: see text]. Tissues have the same index if their influx constants are independent of W. Suggested, therefore, is a very simplified [formula: see text], which is dimensionless and keeps the same population averages as traditional SUVs. It achieves [formula: see text]. Hence, for cv's of SUVs below approximately 1/3 improvements over tradition are possible, leading to F's<0.95. Accounting additionally for height, as in SUVbsa, gives very little improvement over the simplified approach here and gives essentially the same F's as SUVm. Introduced here is a weight index useful in reducing variability and further understanding the SUV. Addressing weight sensitivity is appropriate where the cv of the SUVs is below about 1/3. Proposed is the very simple approach of using an average of an adult patient's weight and approximately 70 kg for FDG SUV calculations. Unlike other approaches the dimensionless population average of SUVms is unchanged from tradition.
    Molecular Imaging & Biology 01/2007; 9(2):91-8. · 3.10 Impact Factor
  • Joseph A Thie
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    ABSTRACT: A region's early and late tracer uptake activities, QE and QL, within a dual-time scan (i.e. using two frames) or in serial scans (as for monitoring therapeutic response), are popular quantitative diagnostic aids, especially in oncology. In this paper, maximum performance is sought from their joint use. QL/QnE is introduced as a tumor marker with an empirical n. This generalizes traditional data weighting having n=1 for QL/QE, the retention index (RI), with its associated % difference. Using patient data, iterative guessing finds an optimal n that maximizes a measure of diagnostic performance: D=(difference of normal and abnormal marker means)/(their combined SD), which may be computed from values of QL/QnE, as well as of QL, QE, and RI each used alone. For 2-deoxy-2-[F-18]fluoro-D-glucose(FDG)-positron emission tomography (PET) dual-time protocols, another approach to optimization-selection of scan times-is investigated by simulations using the Sokolov model. A meta-analysis of 12 PET and single photon emission computed tomography (SPECT) studies with various tracers, cancers, and scan classes (dual-time or serial) finds ns from 0.5 to 1.1. The optimal D necessarily exceeds the best (or any) computed using QE, QL, or RI: negligibly to by as much as 0.6 (or 1.5). The increases in optimal receiver operating curve area (Az) over the best (or any) traditional marker range from negligible to 0.07 (or 0.4). QE alone usually has the lowest D and Az. Statistically significant performance improvement of QL/QnE over QE and QL is shown for most studies. Contrasting with an optimal n, another value n0 can also be found where D=0. Occasionally, n0 can be close to 1, and RI then will have a small D and poor performance. Simulation with kinetic modeling of FDG dual-time scans for liver and liver metastases demonstrates worst and best scan times. Indicated for these imaging protocols are QE at very early cellular transport associated times and QL rather late when phosphorylation/dephosphorylation dominate. Benefits from choosing optimal times in dual-time protocols, especially in combination with choosing optimal ns, can be significant. A protocol-dependent optimizing parameter n in an improved classification marker can easily be identified in a learning set of scans having normals and abnormals. Finding this parameter below 1.0 in most all studies suggests that a popularly used QL/QE may often overweight early activities. Additionally, QL/QE may sometimes be a poor marker choice and underestimate a protocol's diagnostic capability. Subsequent use of the proposed QL/QnE in settings similar to that of the learning set gives improved diagnostic performance over traditional approaches, although by widely varying amounts. Additionally, a method of seeking optimal scan times is demonstrated and suggests significant gains in dual-time protocol performances are possible.
    Molecular Imaging & Biology 01/2007; 9(6):348-56. · 3.10 Impact Factor
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    Joseph A Thie
    Journal of Nuclear Medicine 12/2006; 47(11):1901-2; author reply 1902. · 5.77 Impact Factor
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    ABSTRACT: The aim of this prospective study was to assess the safety and tumor response of intra-arterial Y-90 microspheres for the treatment of surgically unresectable and chemotherapy-refractory liver metastases. Forty-six (46) patients with metastatic cancer to the liver from various solid tumors, with tumor progression despite polychemotherapy, were included. All patients had baseline computed tomography (CT), 18-Fluoro-2-deoxy-D-glucose-positron emission tomography (F-18 FDG-PET), hepatic angiography, and intra-arterial Tc-99m macroaggregated albumin (MAA) scan for the assessment of extrahepatic aberrant perfusion and lung shunting fraction. Twenty-seven (27) and 19 patients were treated with Y-90 glass- or resin-based microspheres (but not both), respectively, on a lobar basis and were monitored over 3 months after last treatment using dedicated attenuation corrected PET. For each patient, regions of interest (ROIs) were drawn along the liver edge to measure total liver standard uptake value (SUV) on axial images covering the entire liver for comparing pre- and post-treatment total liver SUV change. There was a significant decrement in total liver SUV after treatment by either glass- or resin-based microspheres (p = 0.0013 and 0.028, respectively). There was no significant difference in the amplitudes of the mean percentage reduction of tumor metabolism between these two agents (20% +/- 25% vs. 10% +/- 30% for glass- vs. resin-based microspheres; p = 0.38). None of the patients in the glass-based group developed complications, whereas 3 patients had complications related to hyperbilirubinemia (1 transient and 2 permanent) in the resin-based group. Results suggest that there is significant mean reduction of hepatic metastatic tumor load (metabolism), as evaluated objectively by PET after Y-90 microsphere, for the treatment of unresectable metastatic disease to the liver. The Y-90 therapy provides encouraging and safe results by arresting the progression of metastatic cancer to the liver with decreasing tumor metabolism.
    Cancer Biotherapy and Radiopharmaceuticals 09/2006; 21(4):305-13. · 1.74 Impact Factor
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    ABSTRACT: To address glucose sensitivity in lung cancers before and after radiation treatment (Tx). Twelve patients were each studied with two pre-Tx positron emission tomography (PET) scans and 3 patients each with one post-Tx PET scan, with glucose concentration [Glc] and maximum standard uptake value (SUV) recorded. The pre-Tx glucose sensitivity, g from SUV1/SUV2= {[Glc]1/[Glc]2}g and Tx index, tau from SUVpost-Tx/SUVpre-Tx = {[Glc]post-Tx/[Glc]pre-Tx}tau was calculated by linear regression. Pre-Tx SUVs were corrected to post-Tx Glc with g (SUV'pre-Tx) for a pure Tx effect, R = ln(SUVpost-Tx/SUV'pre-Tx). There were no significant differences in SUV but [Glc] were different (96.4 +/- 10.9 vs. 88.3 +/- 10.5, p = 0.015) between two pre-Tx PET scans. Linear regression yielded g = -0.79 and tau = -1.78 to -2.41 (p < 0.0005 in all). The %DeltaSUV after Tx for 3 patients without vs. with g correction were different by -12%, 0%, and + 7%, suggesting varying effects from glucose. R values were also different and mean R (-0.81 +/- 0.38) was significantly different from zero (p = 0.03), consistent with successful Tx as confirmed by clinico-radiologic follow-up. The extra dimension of glucose sensitivity, g besides SUV incorporated in the combined Tx-derived tau may be a useful global Tx evaluation index even with differing [Glc].
    International Journal of Radiation OncologyBiologyPhysics 05/2006; 65(1):132-7. · 4.52 Impact Factor
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    ABSTRACT: The definite evaluation of the regional cerebral heterogeneity using perfusion and metabolism by a single modality of PET imaging has not been well addressed. Thus a statistical analysis of voxel variables from identical brain regions on metabolic and perfusion PET images was carried out to determine characteristics of the regional heterogeneity of F-18 FDG and O-15 H2O cerebral uptake in normal subjects. Fourteen normal subjects with normal CT and/or MRI and physical examination including MMSE were scanned by both F-18 FDG and O-15 H2O PET within same day with head-holder and facemask. The images were co-registered and each individual voxel counts (Q) were normalized by the global maximal voxel counts (M) as R = Q/M. The voxel counts were also converted to z-score map by z = (Q - mean)/SD. Twelve pairs of ROIs (24 total) were systematically placed on the z-score map at cortical locations 15-degree apart and identically for metabolism and perfusion. Inter- and intra-subject correlation coefficients (r) were computed, both globally and hemispherically, from metabolism and perfusion: between regions for the same tracer and between tracers for the same region. Moments of means and histograms were computed globally along with asymmetric indices as their hemispherical differences. Statistical investigations verified with data showed that, for a given scan, correlation analyses are expectedly alike regardless of variables (Q, R, z) used. The varieties of correlation (r's) of normal subjects, showing symmetry, were mostly around 0.8 and with coefficient of variations near 10%. Analyses of histograms showed non-Gaussian behavior (skew = -0.3 and kurtosis = 0.4) of metabolism on average, in contrast to near Gaussian perfusion. The co-registered cerebral metabolism and perfusion z maps demonstrated regional heterogeneity but with attractively low coefficient of variations in the correlation markers.
    BMC Nuclear Medicine 02/2006; 6:4.
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    ABSTRACT: Our objective was to derive the best glucose sensitivity factor (g-value) and the most discriminating standardized uptake value (SUV) normalized to glucose for classifying indolent and aggressive lymphomas. The maximum SUV obtained from (18)F-FDG PET over the area of biopsy in 102 patients was normalized by serum glucose ([Glc]) to a standard of 100 mg/dL. Discriminant analysis was performed by using each SUV(100) (SUV x {100/[Glc]}(g), calculated using various g-values ranging from -3.0 to 0, one at a time) as a variable against the lymphoma grades, and plotting the percentage of correct classifications against g (g-plot) to search for the best g-value in normalizing SUV(100) for classifying grades. To address the influence of the extreme glucose conditions, we repeated the same analyses in 12 patients with [Glc] < or = 70 mg/dL or [Glc] > or = 110 mg/dL. SUV(100) correctly classified lymphoma grades ranging from 62% to 73% (P < 0.0005), depending on the g-value, with a maximum at a g-value of -0.5. For the subgroup with extreme glucose values, the g-plot also revealed higher and more optimal discrimination at a g-value of -0.5 (92%) than at a g-value of 0 (83%) (P = 0.03). The discrimination deteriorated at g < -1 in both analyses. The box plot for all cases using a g-value of -0.5 showed little overlap in classifying lymphoma grades. For a visually selected threshold SUV(100) of 7.25, the sensitivity, specificity, and accuracy of identifying aggressive grades were 82%, 79%, and 81%, respectively. The results suggest that metabolic discrimination between lymphoma grades using a glucose-normalized SUV from (18)F-FDG PET is improved by introducing g-value as an extra degree of freedom.
    Journal of Nuclear Medicine 10/2005; 46(10):1659-63. · 5.77 Impact Factor
  • Joseph A Thie, Gary T Smith, Karl F Hubner
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    ABSTRACT: The positron emission tomography (PET) clinical utility of the sensitivity (gamma) of uptake (Q) to a change in plasma glucose concentration (C) is investigated. Gamma is obtained from data as [ln(Q (2)/Q (1))] / [ln(C(2)/C(1))], using previously published intrapatient studies varying C within a single patient and some interpatient ones. It can be theoretically related to the half-saturation constant in the Michaelis-Menten quantification of competitive uptake. One of its uses is making uptake corrections for desired vs. actual C using Q(2) = Q(1) (C(2)/C(1))(gamma). Intrapatient studies proved to be preferable to interpatient ones, and a 2-deoxy-2-[F-18]fluoro-D-glucose (FDG)-PET survey with analyses for gamma yielded the following result: usually the gamma values of tumors and brain tissues were near -1, whereas those of other noncerebral tissues were near 0. Regarding correcting uptakes for C, instead of a universally assumed and applied gamma = -1, corrections should be for a single tissue using its known gamma. An advantageous use of gamma is predicting how C affects image contrast, including where glucose loading is sometimes preferable to fasting. A potentially useful quantifier of uptake sensitivity to plasma glucose has been defined and values obtained. Correcting uptakes to some standard C requires special care. gamma can help PET clinicians select fasting or loading to achieve glucose levels for optimum contrast.
    Molecular Imaging & Biology 01/2005; 7(5):361-8. · 3.10 Impact Factor
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    Joseph A Thie
    Journal of Nuclear Medicine 10/2004; 45(9):1431-4. · 5.77 Impact Factor
  • Joseph A Thie
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    ABSTRACT: Multiple strategies in diagnoses of different diseases from images can include their histogram analyses. Any fractal behavior in the latter is to be quantified as to extent here, with a view toward contributing to a diagnostic process. One tool in quantitative image analyses is the fractal dimension D of the pixel histogram, a measure of self-similarity over various scales in a fitted power-law behavior of pixel intensity cumulative probability distribution. Proposed and developed here as diagnostic markers are features of its determination process that indicate to what extent there is fractal behavior. One of these is the curvature c that exists in log-log plots used for extracting the fractal exponent D of power-law behavior. Specific implementations are given both for a general lognormal pixel intensity distribution and for lung images. Both Ds and cs are determined for: normals, pulmonary embolism, cystic fibrosis, as well as a theoretical lognormal distribution. It is shown that D and heterogeneity described by a standard deviation are reciprocally related and not typically independent markers. The added independent information from c has possibilities of assisting in discrimination of normal and pathologic conditions, such as in lung diseases. In addition to a histogram's fractal dimension itself, there are indications that measures of the degree of fractal behavior may also hold promise in image diagnoses.
    Molecular Imaging & Biology 01/2003; 5(4):227-31. · 3.10 Impact Factor
  • Radiology 01/2003; 228(1):292-293. · 6.34 Impact Factor
  • Joseph A Thie, Karl F Hubner, Gary T Smith
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    ABSTRACT: The potential for improving the diagnostic performance of static positron imaging tomography (PET) by judiciously choosing optimum post-injection imaging times is investigated. Dynamic and whole-body scan data, from 2-deoxy-2-[18F]fluoro-D-glucose (FDG) oncological studies, are analyzed for changing standardized uptake value (SUV) behavior with increasing post-injection times at either single- or multiple-bed positions. Model-based interpretations address d(SUV)/dt, shown to correlate with SUV, and the contrast ratio for a tumor and its surroundings. A method for correcting measurements to a standardized time is given. Both data and model-based equations suggest that starting data acquisition later than the average 55 +/- 15 (SD) minutes post-injection reported in the FDG literature can improve contrast ratios. Considerations for choosing an optimum time from a clinical standpoint are listed. It is concluded that the appropriate time for each particular protocol can be found with the aid of the information presented here. True optimization, however, remains a complex issue.
    Molecular Imaging & Biology 06/2002; 4(3):238-44. · 3.10 Impact Factor
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    J A Thie, K F Hubner, G T Smith
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    ABSTRACT: A meta-analysis of data primarily from PET oncologic investigations using FDG PET was performed. Its purpose was to establish statistical features of the distributions of standardized uptake values (SUVs) as possible aids in the diagnostic process. We obtained 1536 values of oncologic markers from patient studies of 40 investigations in the literature. Statistical parameters were tabulated for analysis. A significant observation is that, unlike skewed SUV histograms, log10SUV has Gaussian behavior, which is not uncommon for biologic quantities. This was found for SUVs of FDG and 2 amino acids as well as a few other cancer markers. A possible model for explaining this is proposed. For FDG, the SD sigma of the log10SUVs for an average cancer category was 0.23. Examining data within the framework of the model points to physiologic factors as dominating SUV variability rather than PET protocols. When data for a single cancer category were available from multiple institutions, averages, mean(SUV)s, disagree beyond chance expectations. Diagnostic utility suggestions include a universal linear relationship between sensitivity and severity, defined as SUV/mean(SUV), on semilogarithmic probability paper; a generic receiver-operating-characteristic curve for all cancers; using [log10(mean(SUVmal)/mean(SUVnorm))] divided by (sigma(mal)2 + sigma(norm)2)(1/2) as a simple diagnostic effectiveness measure; and using Gaussian log10SUVs to avoid erroneous P values. Using the logarithms of markers, such as SUVs, several advantages stemming from their Gaussian nature can be achieved with benefits ensuing to the diagnostic process.
    Journal of Nuclear Medicine 11/2000; 41(10):1664-72. · 5.77 Impact Factor
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    ABSTRACT: This retrospective study was done to evaluate the utility of 2-[F-18]fluoro-2-deoxy-D-glucose positron emission tomography (F-18-FDG PET) in identifying primary and recurrent breast cancer and lymph node metastases. One hundred whole-body PET scans of 87 patients were reviewed. PET results obtained with F-18-FDG and an ECAT/EXACT-921 or an ECAT-931 (Siemens/CTI) were based on visual interpretation, or standardized uptake values (SUVs), related to histology and also compared to computerized tomography (CT) and mammography results. The sensitivity for PET in detecting primary (N = 35 studies) and recurrent breast cancer (N = 65 studies) was 96% and 85% with a specificity of 91% and 73%. The sensitivity for lymph node metastases at the time of initial diagnosis was 100% with a specificity of 100%. Quantitative SUV information did not improve the accuracy of F-18-FDG PET in identifying primary breast cancers. The results suggest that whole-body PET is useful in detecting recurrence or metastases, may be useful in detecting lymph node metastases prior to initial axillary lymph node dissection, but is less sensitive in excluding axillary lymph nodes metastases later in the course of the disease.
    Clinical Positron Imaging 10/2000; 3(5):197-205.
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    ABSTRACT: Positron emission tomography (PET) using F-18-fluoro-2-deoxy-d-glucose(F-18-FDG) is gaining acceptance as a useful imaging method for head and neck tumors. Results of 59 PET scans done on 45 patients with head and neck tumors were evaluated retrospectively. Thirty-six patients had prior treatment consisting of surgery, radiation therapy, chemotherapy, or a combination of these modalities. PET results were compared to computed tomography and magnetic resonance imaging results and validated by histologic findings or survival. PET identified 36 out of 37 tumors (sensitivity 97%) and 18 of 22 benign processes (specificity 82%). Tumor was ruled out in 18 out of 19 patients. For CT, the sensitivity was 80% (20/25) and specificity was 31% (4/13). FDG-PET facilitates differentiation of recurrent head and neck tumors from treatment related changes sometimes difficult to characterize by CT or MRI and may have a significant impact on the management of patients reducing morbidity and costs.
    Clinical Positron Imaging 02/2000; 3(1):7-16.

Publication Stats

440 Citations
85.58 Total Impact Points

Institutions

  • 1997–2013
    • University of Tennessee
      • Department of Nuclear Engineering
      Knoxville, Tennessee, United States
  • 1998–2010
    • The University of Tennessee Medical Center at Knoxville
      • Department of Radiology
      Knoxville, Tennessee, United States
  • 2005
    • William Beaumont Army Medical Center
      El Paso, Texas, United States