Charles M. Laymon

A fission ionization detector for neutron flux measurements at a spallation source

Abstract The construction of a neutron flux monitor that can measure absolute neutron intensities in the neutron energy range from below 1 MeV to over 500 MeV is described. The detector consists of an ionization chamber with several thin deposits of fissionable material. The ionization chamber is thin enough that it does not significantly affect the neutron beam and may be left in the neutron flight path during experimental measurements to continuously monitor the beam flux. The use of this monitor at the continuous-energy spallation neutron source at the WNR target area at LAMPF is described.

A Comparative Evaluation of the Dopamine D2/3 Agonist Radiotracer [11C](−)-N-Propyl-norapomorphine and Antagonist [11C]Raclopride to Measure Amphetamine-Induced Dopamine Release in the Human Striatum

(−)-N-Propyl-norapomorphine (NPA) is a full dopamine D2/3 receptor agonist, and [11C]NPA is a suitable radiotracer to image D2/3 receptors configured in a state of high affinity for agonists with positron emission tomography (PET). In this study, the vulnerability of the in vivo binding of [11C]NPA to acute fluctuation in synaptic dopamine was assessed with PET in healthy humans and compared with that of the reference D2/3 receptor antagonist radiotracer [11C]raclopride. Ten subjects (eight females and two males) were studied on two separate days, a minimum of 1 week apart, both with [11C]raclopride and [11C]NPA at baseline and after the administration of 0.5 mg · kg−1 oral d-amphetamine. Kinetic modeling with an arterial input function was used to derive the binding potential relative to nonspecific uptake (BPND) in the ventral striatum (VST), caudate (CAD), and putamen (PUT). [11C]Raclopride BPND was significantly reduced by 9.7 ± 4.4, 8.4 ± 4.2, and 14.7 ± 4.8% after amphetamine administration in the VST, CAD, and PUT. [11C]NPA BPND was also reduced significantly, by 16.0 ± 7.0, 16.1 ± 6.1, and 21.9 ± 4.9% after the same dose of amphetamine in the VST, CAD, and PUT. Although these results suggest that [11C]NPA is more vulnerable to endogenous competition by dopamine compared with [11C]raclopride by a factor of 1.49 to 1.90, the same data for a related outcome measure, binding potential relative to plasma concentration, was not significant. Nevertheless, these data add to the growing literature that suggests D2/3 agonist radiotracers are more vulnerable to endogenous competition by dopamine than existing D2/3 antagonist radiotracers.

Infection Dynamics and Response to Chemotherapy in a Rabbit Model of Tuberculosis using [18F]2-Fluoro-Deoxy-d-Glucose Positron Emission Tomography and Computed Tomography

ABSTRACT With a host of new antitubercular chemotherapeutics in development, methods to assess the activity of these agents beyond mouse efficacy are needed to prioritize combinations for clinical trials. Lesions in Mycobacterium tuberculosis-infected rabbits are hypoxic, with histopathologic features that closely resemble those of human tuberculous lesions. Using [18F]2-fluoro-deoxy-d-glucose ([18F]FDG) positron emission tomography–computed tomography (PET-CT) imaging, we studied the dynamics of tuberculosis infection in rabbits, revealing an initial inflammatory response followed by a consolidative chronic disease. Five weeks after infection, as much as 23% of total lung volume was abnormal, but this was contained and to some extent reversed naturally by 9 weeks. During development of this chronic state, individual lesions in the same animal had very different fates, ranging from complete resolution to significant progression. Lesions that remained through the initial stage showed an increase in volume and tissue density over time by CT. Initiation of chemotherapy using either isoniazid (INH) or rifampin (RIF) during chronic infection reduced bacterial load with quantitative changes in [18F]FDG uptake, lesion density and total lesion volume measured by CT. The [18F]FDG PET uptake in lesions was significantly reduced with as little as 1 week of treatment, while the volume and density of lesions changed more slowly. The results from this study suggest that rabbits may be a useful surrogate species for evaluating novel chemotherapies and understanding changes in both PET and CT scans in human clinical trials.

Inter-rater reliability of manual and automated region-of-interest delineation for PiB PET

A major challenge in positron emission tomography (PET) amyloid imaging studies of Alzheimers disease (AD) is the reliable detection of early amyloid deposition in human brain. Manual region-of-interest (ROI) delineation on structural magnetic resonance (MR) images is generally the reference standard for the extraction of count-rate data from PET images, as compared to automated MR-template(s) methods that utilize spatial normalization and a single set of ROIs. The goal of this work was to assess the inter-rater reliability of manual ROI delineation for PiB PET amyloid retention measures and the impact of CSF dilution correction (CSF) on this reliability for data acquired in elderly control (n=5) and AD (n=5) subjects. The intraclass correlation coefficient (ICC) was used to measure reliability. As a secondary goal, ICC scores were also computed for PiB outcome measures obtained by an automated MR-template ROI method and one manual rater; to assess the level of reliability that could be achieved using different processing methods. Fourteen ROIs were evaluated that included anterior cingulate (ACG), precuneus (PRC) and cerebellum (CER). The PiB outcome measures were the volume of distribution (V(T)), summed tissue uptake (SUV), and corresponding ratios that were computed using CER as reference (DVR and SUVR). Substantial reliability (ICC≥0.932) was obtained across 3 manual raters for V(T) and SUV measures when CSF correction was applied across all outcomes and regions and was similar in the absence of CSF correction. The secondary analysis revealed substantial reliability in primary cortical areas between the automated and manual SUV [ICC≥0.979 (ACG/PRC)] and SUVR [ICC≥0.977/0.952 (ACG/PRC)] outcomes. The current study indicates the following rank order among the various reliability results in primary cortical areas and cerebellum (high to low): 1) V(T) or SUV manual delineation, with or without CSF correction; 2) DVR or SUVR manual delineation, with or without CSF correction; 3) SUV automated delineation, with CSF correction; and 4) SUVR automated delineation, with or without CSF correction. The high inter-rater reliability of PiB outcome measures in primary cortical areas (ACG/PRC) is important as reliable methodology is needed for the detection of low levels of amyloid deposition on a cross-sectional basis and small changes in amyloid deposition on a longitudinal basis.

Standardized uptake value-based evaluations of solitary pulmonary nodules using F-18 fluorodeoxyglucose-PET/computed tomography

ObjectiveCombined positron emission tomography and computed tomography (PET/CT) might improve the accuracy of PET tracer quantification by providing the exact tumour contour from coregistered CT images. We compared various semiquantitative approaches for the characterization of solitary pulmonary nodules (SPNs) using F-18 fluorodeoxyglucose PET/CT. MethodsThe final diagnosis of 49 SPNs (46 patients) was based on histopathology (n=33) or patient follow-up (n=16). The regions of interest (ROIs) were drawn around lesions based on the CT tumour contour and mirrored to the coregistered PET images. Quantification of F-18 fluorodeoxyglucose uptake was accomplished by calculating the standardized uptake value (SUV) using three different methods based on: activity from the maximum-valued pixel within the tumour (SUV-max); the mean ROI activity within the transaxial slice containing the maximum-valued pixel (SUV-mean); and the mean activity over the full tumour volume (SUV-vol). SUVs were corrected for partial volume effects and normalized by body surface area, lean body weight, and blood glucose. Recovery coefficients for partial-volume correction were derived from phantom studies. The ability of various SUVs to differentiate between benign and malignant SPNs was determined by calculating the area under the receiver operating characteristic (ROC) curves. ResultsTwenty-six SPNs were malignant and 23 were benign. The area under the ROC curve was 0.78 for SUV-mean, 0.83 for SUV-max, and 0.78 for SUV-vol. SUV-max and its normalizations yielded the highest area under the ROC curve (0.83–0.85); SUV-mean-partial volume corrected-lean body weight resulted in the lowest area under the ROC curve (0.76). At a specificity of 80%, SUV-max-body surface area provided the highest sensitivity (81%) and accuracy (80%) to detect malignant SPN. Using SUV-max with a cutoff of 2.4 at a specificity of 80% resulted in a sensitivity of 62% (accuracy 71%). ConclusionVarious normalizations applied to SUV-max provided the highest diagnostic accuracy for characterization of SPNs. Quantification methods using the exact tumour contour derived from CT in combined PET/CT imaging (ROI mean activity within a single transaxial slice and mean tumour volume activity) did not result in improved differentiation between benign and malignant SPN. Obtaining SUV-max might be sufficient in the clinical setting.

First use of (18)F-labeled ML-10 PET to assess apoptosis change in a newly diagnosed glioblastoma multiforme patient before and early after therapy.

The authors present the first use of the novel positron emission tomography (PET) apoptosis tracer 18F‐labeled 2‐(5‐fluoro‐pentyl)‐2‐methyl‐malonic acid (18F‐ML‐10) for early‐therapy response assessment of a newly diagnosed glioblastoma multiforme (GBM) patient.

Positron emission tomography imaging of D(2/3) agonist binding in healthy human subjects with the radiotracer [(11)C]-N-propyl-norapomorphine: preliminary evaluation and reproducibility studies.

(−)‐N‐[11C]‐propyl‐norapomorphine (NPA) is a full dopamine D2/3 receptor agonist radiotracer suitable for imaging D2/3 receptors configured in a state of high affinity for agonists using positron emission tomography. The aim of the present study was to define the optimal analytic method to derive accurate and reliable D2/3 receptor parameters with [11C]NPA.

PET imaging reveals distinctive roles for different regional adipose tissue depots in systemic glucose metabolism in nonobese humans

Excess amounts of abdominal subcutaneous (SAT) and visceral (VAT) adipose tissue (AT) are associated with insulin resistance, even in normal-weight subjects. In contrast, gluteal-femoral AT (GFAT) is hypothesized to offer protection against insulin resistance. Dynamic PET imaging studies were undertaken to examine the contributions of both metabolic activity and size (volume) of these depots in systemic glucose metabolism. Nonobese, healthy volunteers (n = 15) underwent dynamic PET imaging uptake of [¹⁸F]FDG at a steady-state (20 mU·m⁻²·min⁻¹) insulin infusion. PET images of tissue [¹⁸F]FDG activity were coregistered with MRI to derive K values for insulin-stimulated rates of fractional glucose uptake within tissue. Adipose tissue volume was calculated from DEXA and MRI. VAT had significantly higher rates of fractional glucose uptake per volume than SAT (P < 0.05) or GFAT (P < 0.01). K(GFAT) correlated positively (r = 0.67, P < 0.01) with systemic insulin sensitivity [glucose disappearance rate (R(d))] and negatively with insulin-suppressed FFA (r = -0.71, P < 0.01). SAT (r = -0.70, P < 0.01) and VAT mass (r = -0.55, P < 0.05) correlated negatively with R(d), but GFAT mass did not. We conclude that rates of fractional glucose uptake within GFAT and VAT are significantly and positively associated with systemic insulin sensitivity in nonobese subjects. Furthermore, whereas SAT and VAT amounts are confirmed to relate to systemic insulin resistance, GFAT amount is not associated with insulin resistance. These dynamic PET imaging studies indicate that both quantity and quality of specific AT depots have distinct roles in systemic insulin resistance and may help explain the metabolically obese but normal-weight phenotype.

The Impact of Arterial Input Function Determination Variations on Prostate Dynamic Contrast-Enhanced Magnetic Resonance Imaging Pharmacokinetic Modeling: A Multicenter Data Analysis Challenge

Pharmacokinetic analysis of dynamic contrast-enhanced (DCE) MRI data allows estimation of quantitative imaging biomarkers such as Ktrans (rate constant for plasma/interstitium contrast reagent (CR) transfer) and ve (extravascular and extracellular volume fraction). However, the use of quantitative DCE-MRI in clinical practice is limited with uncertainty in arterial input function (AIF) determination being one of the primary reasons. In this multicenter study to assess the effects of AIF variations on pharmacokinetic parameter estimation, DCE-MRI data acquired at one center from 11 prostate cancer patients were shared among nine centers. Individual AIF from each data set was determined by each center and submitted to the managing center. These AIFs, along with a literature population averaged AIF, and their reference-tissue-adjusted variants were used by the managing center to perform pharmacokinetic data analysis using the Tofts model (TM). All other variables, including tumor region of interest (ROI) definition and pre-contrast T1, were kept constant to evaluate parameter variations caused solely by AIF discrepancies. Considerable parameter variations were observed with the within-subject coefficient of variation (wCV) of Ktrans obtained with unadjusted AIFs being as high as 0.74. AIF-caused variations were larger in Ktrans than ve and both were reduced when reference-tissue-adjusted AIFs were used. These variations were largely systematic, resulting in nearly unchanged parametric map patterns. The intravasation rate constant, kep (= Ktrans/ve), was less sensitive to AIF variation than Ktrans (wCV for unadjusted AIFs: 0.45 vs. 0.74), suggesting that it might be a more robust imaging biomarker of prostate microvasculature than Ktrans.

PET/CT artifacts

There are several artifacts encountered in positron emission tomography/computed tomographic (PET/CT) imaging, including attenuation correction (AC) artifacts associated with using CT for AC. Several artifacts can mimic a 2-deoxy-2-[18F] fluoro-d-glucose (FDG) avid malignant lesions and therefore recognition of these artifacts is clinically relevant. Our goal was to identify and characterize these artifacts and also discuss some protocol variables that may affect image quality in PET/CT.