An empirical artifact correction for proton computed tomography

Purpose: To reduce image artifacts of proton computed tomography (pCT) from a preclinical scanner, for imaging of the relative stopping power (RSP) needed for particle therapy treatment planning using a simple empirical artifact correction method.Methods: We adapted and employed a correction method previously used for beam-hardening correction in x-ray CT which makes use of a single scan of a custom-built homogeneous phantom with known RSP. Exploiting the linearity of the filtered backprojection operation, a function was found which corrects water-equivalent path lengths (RSP line integrals) in experimental scans using a prototype pCT scanner. The correction function was applied to projection values of subsequent scans of a homogeneous water phantom, a sensitometric phantom with various inserts and an anthropomorphic head phantom. Data were acquired at two different incident proton energies to test the robustness of the method.Results: Inaccuracies in the detection process caused an offset and known ring artifacts in the water phantom which were considerably reduced using the proposed method. The mean absolute percentage error (MAPE) of mean RSP values of all inserts of the sensitometric phantom and the water phantom was reduced from 0.87% to 0.44% and from 0.86% to 0.48% for the two incident energies respectively. In the head phantom a clear reduction of artifacts was observed.Conclusions: Image artifacts of experimental pCT scans with a prototype scanner could substantially be reduced both in homogeneous, heterogeneous and anthropomorphic phantoms. RSP accuracy was also improved.     

Kidney pseudotumour diagnosed by emission computed tomography.

Emission computed tomography is a new, useful imaging technique; when a rotating gamma camera capable of such imaging is used multiple adjacent transverse sections may be obtained simultaneously, from which coronal and sagittal sections may be computed. The technique was used in a man undergoing urological investigation in whom excretion urography indicated a space-occupying lesion in the left kidney. Ultrasonography and radionuclide imaging showed nothing abnormal, but emission computed tomography using a rotating gamma camera showed that functioning cortical tissue extended across the middle of the left kidney. Radiographs were therefore reviewed and ultrasonography repeated, and it was concluded that the abnormality was a hypertrophied column of Bertin. Emission tomographic imaging of the kidney is a useful adjunct to other non-invasive studies.     

Small-animal imaging using clinical positron emission tomography/computed tomography and super-resolution

Considering the high cost of dedicated small-animal positron emission tomography/computed tomography (PET/CT), an acceptable alternative in many situations might be clinical PET/CT. However, spatial resolution and image quality are of concern. The utility of clinical PET/CT for small-animal research and image quality improvements from super-resolution (spatial subsampling) were investigated. National Electrical Manufacturers Association (NEMA) NU 4 phantom and mouse data were acquired with a clinical PET/CT scanner, as both conventional static and stepped scans. Static scans were reconstructed with and without point spread function (PSF) modeling. Stepped images were postprocessed with iterative deconvolution to produce super-resolution images. Image quality was markedly improved using the super-resolution technique, avoiding certain artifacts produced by PSF modeling. The 2 mm rod of the NU 4 phantom was visualized with high contrast, and the major structures of the mouse were well resolved. Although not a perfect substitute for a state-of-the-art small-animal PET/CT scanner, a clinical PET/CT scanner with super-resolution produces acceptable small-animal image quality for many preclinical research studies.     

Mechanism of mosaic attenuation of the lungs on computed tomography in induced bronchospasm

The purpose of this study was to investigatewhether hypoxic pulmonary vasoconstriction is the major determinant ofthe computed tomography (CT) pattern of mosaic attenuation in asthmaticpatients with induced bronchoconstriction. Thin-section CT wasperformed at suspended full inspiration immediately and 30 min aftermethacholine bronchoprovocation in 22 asthmatic subjects, who wererandomly assigned to breathe room air (group A,n = 8), oxygen via nasal prongs at 5 l/min (group B,n = 8), and oxygen via face mask at 12 l/min (group C,n = 6). CT changes were quantified interms of global lung density and density in hypodense and hyperdense areas. Lung parenchymal density increases were greatest ingroup C and greater ingroup B than in groupA, globally (P = 0.03) and in hypodense regions (P = 0.01).On bivariate analysis, the only change in cross-sectional area wasrelated to change in global density. In hypodense regions, densitychange was related both to reduction in cross-sectional area(P < 0.0005) and to oxygen administration (P = 0.01). Aftercorrection for changes in global lung density, only oxygen wasindependently related to density increase in hypodense areas(P = 0.02). In inducedbronchoconstriction, the CT appearance of mosaic attenuation can belargely ascribed to hypoxic vasoconstriction rather than to changes inlung inflation.     

Magnetic resonance tomography, computed tomography and ultrasonic diagnosis of hemangiomas of the liver

The paper is concerned with the potentialities of modern radiation methods in the diagnosis of liver hemangiomas. USI, CT, angiography and MR-tomography (MRT) were used for investigation of 64 patients with liver hemangiomas. The diagnostic potentialities and the role of each of the above methods in the diagnostic algorithm in liver hemangiomas were studied. The results of the investigation have shown that MRT possesses a higher informative value than USI and CT in the diagnosis of liver hemangiomas and can even replace angiography in the verification of diagnosis.     

Comparison between emission and transmission computed tomography of the liver.

Emission computed tomography (emission CT) and conventional planar gamma-camera imaging of the liver were compared in 242 patients with suspected metastatic spread to liver. Concordant data were obtained in 171 patients (71%). Single large lesions, multiple small lesions, and diffuse disease were accurately defined with this new radionuclide tomographic technique. The smallest lesion detected by emission CT was 8 mm. Emission CT, planar gamma-camera imaging, and transmission (x-ray) CT were compared in 107 patients. All three methods gave identical results in 76 patients (71%). Assessed against other criteria, such as histological findings and follow-up data, emission CT yielded the highest range of accuracy (92-96%), while transmission CT and planar gamma-camera imaging had similar but lower accuracies (78-81%). Emission CT had a false-positive rate of 2.8% and a false-negative rate of less than 1%. Thus emission CT is highly sensitive in detecting space-occupying disease in the liver.     

Organ-specific dietary fatty acid uptake in humans using positron emission tomography coupled to computed tomography

A noninvasive method to determine postprandial fatty acid tissue partition may elucidate the link between excess dietary fat and type 2 diabetes. We hypothesized that the positron-emitting fatty acid analog 14(R,S)-[(18)F]fluoro-6-thia-heptadecanoic acid ((18)FTHA) administered orally during a meal would be incorporated into chylomicron triglycerides, allowing determination of interorgan dietary fatty acid uptake. We administered (18)FTHA orally at the beginning of a standard liquid meal ingested in nine healthy men. There was no significant (18)FTHA uptake in the portal vein and the liver during the 1st hour. Whole body PET/CT acquisition revealed early appearance of (18)FTHA in the distal thoracic duct, reaching a peak at time 240 min. (18)FTHA mean standard uptake value increased progressively in the liver, heart, quadriceps, and subcutaneous and visceral adipose tissues between time 60 and 240 min. Most circulating (18)F activity between time 0 and 360 min was recovered into chylomicron triglycerides. Using Triton WR-1339 treatment in rats that received (18)FTHA by gavage, we confirmed that >90% of this tracer reached the circulation as triglycerides. This novel noninvasive method to determine tissue dietary fatty acid distribution in humans should prove useful in the study of the mechanisms leading to lipotoxicity.     

Strategies for the labeling of halogen-substituted peroxisome proliferator-activated receptor gamma ligands: potential positron emission tomography and single photon emission computed tomography imaging agents

Well-known as an important regulator of lipid metabolism and adipocyte differentiation, the peroxisome proliferator-activated receptor gamma (PPARgamma) also has potential use as a target for antitumor therapy in certain cancers. To develop agents for radionuclide imaging PPARgamma in vivo, we synthesized fluorine, bromine, and iodine-substituted analogs (1-3) of a high-affinity benzophenone-tyrosine PPARgamma ligand; all three analogs retain very high affinity for the PPARgamma receptor. In preparation for the synthesis of these PPARgamma ligands in radiolabeled form, we have synthesized two types of precursors: (a) an aryltributylstannane (9), from which the bromine and iodine-substituted analogs (2 and 3) can readily be prepared by electrophilic destannylation, and (b) three diaryliodonium tosylate derivatives (12a-c), precursors for nucleophilic aromatic fluorination using fluoride ion. Conditions were developed whereby the thiophenyliodonium tosylate (12c) underwent nucleophilic aromatic substitution with fluoride ion, efficiently and in short reaction times, to produce the desired fluorine-substituted target compound 1. These reactions laid the groundwork for producing these three PPARgamma ligands in radiolabeled form; in addition, our use of diaryliodonium ion precursors for aromatic fluorination in this series provides an example that should encourage application of this approach for radiofluorination of more complicated radiopharmaceuticals.     

Integrated 18F-fluorodeoxyglucose-positron emission tomography/dynamic contrast-enhanced computed tomography to phenotype non-small cell lung carcinoma

AbstractWe applied modern molecular and functional imaging to the pretreatment assessment of lung cancer using combined dynamic contrast-enhanced computed tomography (DCE-CT) and 18F-fluorodeoxyglucose-positron emission tomography (18F-FDG-PET) to phenotype tumors. Seventy-four lung cancer patients were prospectively recruited for 18F-FDG-PET/DCE-CT using PET/64-detector CT. After technical failures, there were 64 patients (35 males, 29 females; mean age [± SD] 67.5 ± 7.9 years). DCE-CT yielded tumor peak enhancement (PE) and standardized perfusion value (SPV). The uptake of 18F-FDG quantified on PET as the standardized uptake value (SUVmax) assessed tumor metabolism. The median values for SUVmax and SPV were used to define four vascular-metabolic phenotypes. There were associations (Spearman rank correlation [rs]) between tumor size and vascular-metabolic parameters: SUVmax versus size (rs = .40, p = .001) and SUV/PE versus size (r = .43, p < .001). Patients with earlier-stage (I-IIA, n = 30) disease had mean (± SD) SUV/PE 0.36 ± 0.28 versus 0.56 ± 0.32 in later-stage (stage IIB-IV, n = 34) disease (p = .007). The low metabolism with high vascularity phenotype was significantly more common among adenocarcinomas (p = .018), whereas the high metabolism with high vascularity phenotype was more common among squamous cell carcinomas (p = .024). Other non-small cell lung carcinoma tumor types demonstrated a high prevalence of the high metabolism with low vascularity phenotype (p = .028). We show that tumor subtypes have different vascular-metabolic associations, which can be helpful clinically in managing lung cancer patients to hone targeted therapy.     

Experimental evaluation of depth-of-interaction correction in a small-animal positron emission tomography scanner

Human and small-animal positron emission tomography (PET) scanners with cylindrical geometry and conventional detectors exhibit a progressive reduction in radial spatial resolution with increasing radial distance from the geometric axis of the scanner. This "depth-of-interaction" (DOI) effect is sufficiently deleterious that many laboratories have devised novel schemes to reduce the magnitude of this effect and thereby yield PET images of greater quantitative accuracy. Here we examine experimentally the effects of a particular DOI correction method (dual-scintillator phoswich detectors with pulse shape discrimination) implemented in a small-animal PET scanner by comparing the same phantom and same mouse images with and without DOI correction. The results suggest that even this relatively coarse, two-level estimate of radial gamma ray interaction position significantly reduces the DOI parallax error. This study also confirms two less appreciated advantages of DOI correction: a reduction in radial distortion and radial source displacement as a source is moved toward the edge of the field of view and a resolution improvement detectable in the central field of view likely owing to improved spatial sampling.     

Skeletal muscle attenuation determined by computed tomography is associated with skeletal muscle lipid content.

The purpose of this investigation was to validate that in vivo measurement of skeletal muscle attenuation (MA) with computed tomography (CT) is associated with muscle lipid content. Single-slice CT scans performed on phantoms of varying lipid concentrations revealed good concordance between attenuation and lipid concentration (r(2) = 0.995); increasing the phantom's lipid concentration by 1 g/100 ml decreased its attenuation by approximately 1 Hounsfield unit (HU). The test-retest coefficient of variation for two CT scans performed in six volunteers was 0.51% for the midthigh and 0.85% for the midcalf, indicating that the methodological variability is low. Lean subjects had significantly higher (P < 0.01) MA values (49.2 +/- 2.8 HU) than did obese nondiabetic (39.3 +/- 7.5 HU) and obese Type 2 diabetic (33.9 +/- 4. 1 HU) subjects, whereas obese Type 2 diabetic subjects had lower MA values that were not different from obese nondiabetic subjects. There was also good concordance between MA in midthigh and midcalf (r = 0.60, P < 0.01), psoas (r = 0.65, P < 0.01), and erector spinae (r = 0.77, P < 0.01) in subsets of volunteers. In 45 men and women who ranged from lean to obese (body mass index = 18.5 to 35.9 kg/m(2)), including 10 patients with Type 2 diabetes mellitus, reduced MA was associated with increased muscle fiber lipid content determined with histological oil red O staining (P = -0.43, P < 0. 01). In a subset of these volunteers (n = 19), triglyceride content in percutaneous biopsy specimens from vastus lateralis was also associated with MA (r = -0.58, P = 0.019). We conclude that the attenuation of skeletal muscle in vivo determined by CT is related to its lipid content and that this noninvasive method may provide additional information regarding the association between muscle composition and muscle function.     

An inexpensive approach to improving data derived from single photon emission computed tomography

The issue of inadequate solid standards for correcting nonuniformity in single photon emission computed tomography was addressed. Controlled, complex, motion of commercially available cobalt-57 standards was found to enhance the perceived nonuniformity of the standard and to minimize the effects of any local flaws. This maneuver provides a better standard than a refillable liquid phantom without the problems inherent in radioactive liquid standards which include: phantom deformation, poor mixing, absence of retrospective verification, accidental contamination and substantial handling requirements.     

Radiopharmaceutical chemistry for positron emission tomography

Radiopharmaceutical chemistry includes the selection, preparation, and preclinical evaluation of radiolabeled compounds. This paper describes selection criteria for candidates for positron emission tomography (PET) investigations. Practical aspects of nucleophilic and electrophilic (18)F-fluorinations and (11)C-methylations are described. These aspects include production of fluorine-18 and carbon-11, workup of fluorine-18, (18)F radiochemistry, production of [(11)C]methyl iodide and triflate, and (11)C-methylation radiochemistry.     

Genetic alterations associated with 18F-fluorodeoxyglucose positron emission tomography/computed tomography in head and neck squamous cell carcinoma

BackgroundWe investigated the relationship between genetic alterations and ¹⁸F-FDG PET/CT findings in head and neck squamous cell carcinoma (HNSC).MethodsUsing mRNA-sequences of HNSC samples (480 patients) from the Cancer Genome Atlas (TCGA) portal, gene coexpression networks were constructed via a weighted correlation network analysis (WGCNA) algorithm, and their association with the tumor-to-blood signal ratio on ¹⁸F-FDG PET/CT data (21 patients) was explored. An elastic-net regression model was developed to estimate the PET tumor-to-blood ratio from the gene networks and to derive an FDG signature score (FDG_SS). The FDG_SS was evaluated with regard to clinical variables and general mutational profiles, as well as alterations to oncogenic signaling pathways.FindingsThe FDG_SS values differed across clinical stages (p = 0.027), HPV-status (p< 0.001), and molecular subtypes of HNSC (p< 0.001). Multivariate Cox regression demonstrated that FDG_SS was an independent predictor for overall (p = 0.019) and progression-free survival (p = 0.024). FDG_SS positively correlated with total mutation rate (p = 0.016), aneuploidy (p < 0.001), and somatic copy number alteration scores (p < 0.001). CDKN2A in the cell cycle pathway (q = 0.014) and the TP53 gene in the TP53 pathway (q = 0.005) showed significant differences between high and low FDG_SS patients.ConclusionFDG_SS based on the gene coexpression network was associated with the mutational landscape of HNSC. ¹⁸F-FDG PET/CT is therefore a valuable tool for the in vivo imaging of these cancers, being able to visualize the glucose metabolism of the tumor and allow inferences to be made on the underlying genetic alterations in the tumor.