Combined dual energy and iterative metal artefact reduction for PET/CT in head and neck cancer.

Metal artefacts in PET/CT images hamper diagnostic accuracy in head and neck cancer (HNC). The aim of this study is to characterise the clinical effects of metal artefacts on PET/CT in HNC and to inform decision-making concerning implementation of MAR techniques. We study a combined dual energy CT and inpainting-based metal artefact reduction (DECT-I-MAR) technique for PET/CT in three settings: (A) A dental phantom with a removable amalgam-filled tooth to evaluate the PET error in comparison to a known reference. (B) PET-positive patients with metallic implants to demonstrate the relationship between CT metal artefacts and PET error. (C) Metabolic tumour volumes delineated in PET-positive patients with metal implants to evaluate the clinical impact. In (A) DECT-I-MAR reduced the PET error significantly. In (B) we demonstrate an increasing PET error with increasing CT artefact severity in patients. In (C) it is shown that the presence of artefacts in the same axial slices as the tumour significantly decreases biomarker stability and increase delineation variability. This work shows the practical feasibility of DECT-I-MAR-based PET/CT imaging, and indicates a positive clinical impact of using the technique routinely for HNC patients. The impact of CT artefacts on PET is considerable, especially in workflows where quantitative PET biomarkers and tumour volumes are used. In such cases, and for patients with tumours in proximity of metals, we recommend that a MAR technique for PET/CT is employed.

Reproducibility of (18)F-FDG PET uptake measurements in head and neck squamous cell carcinoma on both PET/CT and PET/MR.

OBJECTIVE: To investigate reproducibility of fluorine-18 fludeoxyglucose ((18)F-FDG) uptake on (18)F-FDG positron emission tomography (PET)/CT and (18)F-FDG PET/MR scans in patients with head and neck squamous cell carcinoma (HNSCC). METHODS: 30 patients with HNSCC were included in this prospective study. The patients were scanned twice before radiotherapy treatment with both PET/CT and PET/MR. Patients were scanned on the same scanners, 3 days apart and according to the same protocol. Metabolic tumour activity was measured by the maximum and peak standardized uptake value (SUVmax and SUVpeak, respectively), and total lesion glycolysis from the metabolic tumour volume defined from ≥50% SUVmax. Bland-Altman analysis with limits of agreement, coefficient of variation (CV) from the two modalities were performed in order to test the reproducibility. Furthermore, CVs from SUVmax and SUVpeak were compared. The area under the curve from cumulative SUV-volume histograms were measured and tested for reproducibility of the distribution of (18)F-FDG uptake. RESULTS: 24 patients had two pre-treatment PET/CT scans and 21 patients had two pre-treatment PET/MR scans available for further analyses. Mean difference for SUVmax, peak and mean was approximately 4% for PET/CT and 3% for PET/MR, with 95% limits of agreement less than ±20%. CV was small (5-7%) for both modalities. There was no significant difference in CVs between PET/CT and PET/MR (p = 0.31). SUVmax was not more reproducible than SUVpeak (p = 0.09). CONCLUSION: (18)F-FDG uptake in PET/CT and PET/MR is highly reproducible and we found no difference in reproducibility between PET/CT and PET/MR. ADVANCES IN KNOWLEDGE: This is the first report to test reproducibility of PET/CT and PET/MR.

Whole-body PET/MRI: the effect of bone attenuation during MR-based attenuation correction in oncology imaging.

PURPOSE: In combined PET/MRI standard PET attenuation correction (AC) is based on tissue segmentation following dedicated MR sequencing and, typically, bone tissue is not represented. We evaluate PET quantification in whole-body (WB)-PET/MRI following MR-AC without considering bone attenuation and then investigate different strategies to account for bone tissue in clinical PET/MR imaging. To this purpose, bone tissue representation was extracted from separate CT images, and different bone representations were simulated from hypothetically derived MR-based bone classifications. METHODS: Twenty oncology patients referred for a PET/CT were injected with either [18F]-FDG or [18F]-NaF and imaged on PET/CT (Biograph TruePoint/mCT, Siemens) and PET/MRI (mMR, Siemens) following a standard single-injection, dual-imaging clinical WB-protocol. Routine MR-AC was based on in-/opposed-phase MR imaging (orgMR-AC). PET(/MRI) images were reconstructed (AW-OSEM, 3 iterations, 21 subsets, 4mm Gaussian) following routine MR-AC and MR-AC based on four modified attenuation maps. These modified attenuation maps were created for each patient by non-linear co-registration of the CT images to the orgMR-AC images, and adding CT bone mask values representing cortical bone: 1200HU (cortCT), spongiosa bone: 350HU (spongCT), average CT value (meanCT) and original CT values (orgCT). Relative difference images of the PET following AC using the modified attenuation maps were compared. SUVmean was calculated in anatomical reference regions and for PET-positive lesions. RESULTS: The relative differences in SUVmean across patients following orgMR-AC and orgCT in soft tissue lesions and in bone lesions were similar (range: 0.0% to -22.5%), with an average underestimation of SUVmean of 7.2% and 10.0%, respectively when using orgMR-AC. In bone lesions, spongCT values were closest to orgCT (median bias of 1.3%, range: -9.0% to 13.5%) while the overestimation of SUVmean with respect to orgCT was highest for cortCT (40.8%, range: 1.5% to 110.8%). For soft tissue lesions the bias was highest using cortCT (13.4%, range: -2.3% to 17.3%) and lowest for spongCT (-2.2%, range: 0.0% to -13.7%). CONCLUSIONS: In PET/MR imaging using standard MR-AC PET uptake values in soft lesions and bone lesions are underestimated by about 10%. In individual patients this bias can be as high as 22%, which is significant during clinical follow-up exams. If bone segmentation is available, then assigning a fixed attenuation value of spongious bone to all bone structures appears reasonable and results in only a minor bias of 5%, or less in uptake values of soft tissue and bone lesions.

Innovations in PET/CT.

There has been a longstanding interest in positron emission tomography (PET) in combination with computed tomography (CT). Mostly because of the lack of structural information in PET which makes it difficult to assess the precise location of tissue with metabolic uptake, whereas CT can provide impressive anatomical details. PET/CT designs are facing many challenges such as the conversion of CT numbers to attenuation coefficients, giving rise to artefacts due to the presence of high Zeff material. Patient motion during scans degrades image quality and subsequent analysis, and is a challenge especially as spatial resolution improves. Software based image fusion remains a complex issue outside the brain. State of the art image quality in a modern PET/CT system includes incorporation of point spread function (PSF) and time-of-flight (TOF) information into the reconstruction leading to the high resolution of today's PET/CT systems. This review outlines the background and current knowledge of the PET/CT system design, motion correction and reconstruction approaches.

Enhanced larval cyst growth of Echinococcus multilocularis in praziquantel-treated jirds (Meriones unguiculatus).

Jirds (Meriones unguiculatus) inoculated intraperitoneally with cystic material of Echinococcus multilocularis were given daily oral treatments of praziquantel at 300 mg/kg of body weight (bw) or dimethyl sulfoxide vehicle for five-day treatment regimens starting at 29 days postinoculation (PI) up to 69 days PI. At 39 or 49 days PI, the growth of the larval cystic mass (LCM) in jirds following a single or two five-day treatment regimens was significantly enhanced (P < 0.05) by 129.0% (2.3-fold) or 102.9% (2.0-fold), respectively. At 59 or 69 days PI following three or four five-day treatments with praziquantel, LCM growth was enhanced by 47.8% (1.5-fold) and 44.1% (1.4-fold), respectively, but was no longer significantly different than that in control jirds. A single five-day treatment on 29-33 days PI (with necropsy at 69 days PI) significantly enhanced the growth of the LCM by 87.6% (1.9-fold). Parasites from praziquantel treatment regimens examined ultrastructurally showed consistent damage to the germinal membrane evidenced by vacuolization and rupture of syncytial cytoplasm, rupture and coalescence of the electron-lucent vesicles just below the microvilli of the tegumental surface, and swelling and rounding of mitochondria. At 39 days PI, increased blebbing of the germinal membrane into the lumen of the LCM in praziquantel-treated animals was observed by scanning electron microscopy. The treatment-induced blebs were identified as nucleated germinal cells by transmission electron microscopy and appeared to be responsible for metastasis and enhanced growth of the LCM. Although praziquantel damaged the ultrastructural integrity of the LCM, treatment failed to inhibit larval cyst growth or protoscolex development.(ABSTRACT TRUNCATED AT 250 WORDS)

Frequency distribution of Echinococcus granulosus hydatid cysts in sheep populations in the Xinjiang Uygur Autonomous Region, China.

Age-prevalence and age-intensity data of Echinococcus granulosus hydatid cysts in sheep populations were collected in an abattoir in the Xinjiang Uygur Autonomous Region, People's Republic of China. The frequency distribution of the larval cysts per sheep was empirically described by the negative binomial model, with parameter k being 0.5273. A mathematical model for the life cycle of E. granulosus was applied to the collected data and the results show that the infection pressure on sheep was 0.4362 (female) or 0.4119 (male) infections per year, the mean number of cysts increased linearly by 0.8824 (female) or 0.9971 (male) cysts every year and acquired immunity was too low to depress this rate of increase. According to certain definitions of steady states for taeniid populations, it was concluded that at least in some parts of Xinjiang, the life cycle of E. granulosus was and may still be in an endemic steady state. Consequently, the regular dog-dosing program would readily drive the infection from an endemic state towards extinction.

Frequency distribution of Echinococcus granulosus in dog populations in the Xinjiang Uygur Autonomous Region, China.

Age-prevalence and age-intensity data of Echinococcus granulosus in dog populations were collected in four counties in the Xinjiang Uygur Autonomous Region, People's Republic of China. The frequency distribution of the parasite per dog was adequately described by the negative binomial model, with parameter k being 0.0571. The mathematical model of the life cycle of E. granulosus constructed by Roberts et al. (1986--Parasitology, Vol. 92, pages 621-641) was used to estimate the epidemiologic parameters of E. granulosus in Xinjiang. This model showed that the prevailing infection pressure on dogs was 0.4560 infectious insults year-1 and the mean length of an infection was 1.4975 years. The effect of acquired immunity on the prevalence of E. granulosus in dogs was considered to be insignificant.

Cystic echinococcosis in the Xinjiang/Uygur Autonomous Region, People's Republic of China. II. Comparison of three levels of a local preventive and control program.

A project to compare different levels of a hydatid disease control program was instigated and evaluated in 16 randomly selected villages in the Xinjiang/Uygur Autonomous Region, PRC (China). Factors tested included the effect of: 1) the role of a village hydatid disease control officer, 2) the use of praziquantel-medicated "bait" tablets for treatment of Echinococcus granulosus tapeworms in dogs, and 3) the use of educational materials for children and adults. Evaluation of contrasting treatment levels was done by determining infection rates of E. granulosus in about 25 dogs examined from each of the 16 villages before and after the trial period, and by use of pre- and post-treatment questionnaires distributed to 40 randomly selected households in each village. Optimum results were obtained in those villages which received medicated tablets and support visits from a control officer on a monthly basis (so-called "moderate intervention level").

Immunoglobulin E and G4 antibodies in cysticercosis.

The importance of immunoglobulin G (IgG) subclass responses in different infections has been elucidated for a number of organisms, but few parasitic organisms have been examined in this regard. In the current study, quantitative radioimmunoassays were used to examine the IgE and IgG4 subclass responses to larval Taenia solium. Patients were divided into clinically infected (CI) and probably uninfected (PU) groups. Unexposed normal subjects were used as controls. The CI group had elevated geometric mean levels of total IgE in serum (28.6 IU/ml) and specific IgG4 antibodies (438.8 arbitrary units [AU]/ml) compared with controls (8.3 IU/ml and 50.1 AU/ml, respectively). The CI group also had significantly elevated levels in cerebrospinal fluid of total IgG4 (18.6 micrograms/ml) and specific IgG4 antibodies (86.0 AU/ml) compared with the PU group (2.5 micrograms/ml and 1.6 AU/ml, respectively). There was no specific IgE antibody response detected in either the CI or PU patient group. The marked IgG4 response of CI patients to T. solium merits further investigation.

Cystic echinococcosis in the Xinjiang/Uygur Autonomous Region, People's Republic of China. I. Demographic and epidemiologic data.

Demographic and epidemiologic data on those factors potentially related to the prevalence and transmission of hydatid disease caused by Echinococcus granulosus were collected in 1987 from each household in 85 villages in the two communities of Yuanhucun and Ershilidian within Hutubi County in the Xinjiang/Uygur Autonomous Region, PRC, with additional questionnaire data collected from approximately 40 households randomly selected from each of 16 villages within those communities. Yuanhucun and Ershilidian represent a combined area of 522.7 square km, and have 4,853 households with 25,684 inhabitants. Of those households, 69.9% are of the Han ethnic group, 22.1% Hui, 5.3% Uygur, and 2.7% Kazak. The total number of animals censused included 4,169 dogs, 41,369 sheep, 3,673 goats, 2,639 cattle, 5,400 pigs, 1,472 horses, and 59 donkeys. Levels of infection of the causative organism of cystic hydatid disease in various hosts were: dogs harboring Echinococcus granulosus tapeworms - 63 (16.2%) positive of 390 examined in 16 villages; domestic animals with hydatid cysts - 1,593 (88.6%) sheep of 1,797 examined, 69 (56.1%) of 123 goats, and 47 (94.0%) of 50 cattle; and 15 surgeries in inhabitants from 85 villages during the last 16 months prior to completion of the survey (annual case rate of 43.8/100,000). Questionnaire data collected from inhabitants in 16 villages showed that about 82% of the families owned at least one dog and 78% owned sheep. Of those families with sheep, most (84%) killed sheep for meat at least periodically, 76% had seen hydatid cysts in liver or lungs of butchered animals, and 77% routinely gave raw offal to their dog.(ABSTRACT TRUNCATED AT 250 WORDS)

In vivo efficacy and ultrastructural effects of mitomycin C against experimental alveolar hydatid disease.

The in vivo efficacy and ultrastructural effects of mitomycin C were determined against alveolar hydatid disease in experimentally infected animals and compared to mebendazole treatment. Mitomycin C inhibited the mean cyst mass of treated versus control animals by 84.1% which was statistically significant at the alpha = 0.01 level. Mebendazole given daily inhibited the mean cyst mass by 80.1%, while mebendazole administration on the same treatment schedule as that used for mitomycin C inhibited the mean cyst mass by 70.4%. Ultrastructurally, mitomycin C was not observed to affect the tegumental microtriches (microvilli) or the microtubular system. However, an increase in the number and accumulation of round to oval electrondense vesicles was observed within the subtegument. These inclusion bodies became vacuolated, subsequently degenerated, and formed myelin-like figures. Mitomycin C, like mebendazole, was only cystistatic in its effects on the cyst stage of Echinococcus multilocularis as evidenced by the growth of treated cyst material following inoculation into helminth-free animals.

Efficacy of a combined paste formulation of praziquantel/febantel against immature Echinococcus granulosus and immature Echinococcus multilocularis.

A combined paste formulation of praziquantel (1 mg/kg of body wt)/febantel (10 mg/kg) given for 3 consecutive days gave 100% clearance of immature Echinococcus granulosus and E multilocularis in experimentally infected dogs. The formulation was extremely convenient to administer. Adverse reactions were not noted in the treated animals.

Ultrastructural characterization of serum-induced changes in the tegument of Taenia taeniaeformis.

The objective of this study was to characterize complement-dependent damage to the tegument of isolated metacestodes of Taenia taeniaeformis caused by exposure to immune or normal rat serum (IRS and NRS, respectively). Metacestodes of T. taeniaeformis (34- and 69-day-old) from rats were incubated for 1 hr in 0.85% physiological saline solution (PSS), IRS, NRS, heat-inactivated at 56 C for 1 hr (delta) IRS, or delta NRS and then fixed for 2 hr in 3% glutaraldehyde. The larvae were then prepared for freeze-etching, thin sectioning, and SEM by standard techniques. Freeze-etch replicas of PSS-, delta IRS-, and delta NRS-treated larvae showed no damage, whereas those of IRS- and NRS-treated metacestodes exhibited vesiculation in the extracellular matrices, segmentation or "beading" of the microthrix tip, significant reductions in the number of intramembranous particles (IMP) in the P face of the membrane of the microthrix base, and changes in the pattern of IMP distribution in the P face of the base. Similar results were obtained from larvae prepared for thin sectioning and SEM. Additionally, thin-sectioned preparations demonstrated that in some cases the entire tegument was stripped away in IRS- and NRS-treated metacestodes. Our results have provided supportive evidence that complement-mediated lysis of larvae of T. taeniaeformis is not enhanced by the presence of antibody in serum, and we also characterized ultrastructurally the types of tegumental damage that may contribute to lysis. In addition, a possible defense mechanism used by the parasite to counter immunological attack by host phagocytic cells is proposed.

Fine structure and freeze-etch study of the protoscolex tegument of Echinococcus multilocularis (cestoda).

Freeze-etch replicas of the protoscolex tegument of Echinococcus multilocularis were examined and compared with conventional thin sections by TEM. The microtopography of the protoscolex tegument was also examined by SEM. The protoscolex consisted of morphologically-distinct, apical and basal tegumentary regions, the latter of which lacked microtriches. The hook area of the apical region contained long, slender, filamentous microtriches that obscured the hook arrangement. These microtriches were structurally different from those found on the suckers and rostellum of the protoscolex. Freeze-etch replicas of the tegumental membrane of the sucker and rostellar microtriches showed that the protoplasmic (P) and exoplasmic (E) faces of the microthrix base and tip contained numerous intramembranous particles (IMP). The densities of the IMP on both the P and E faces of the microthrix tip were approximately twice the number of the larger diameter IMP found on the P and E faces of the microthrix base. No freeze-etch replicas of the microtriches from the hook area were obtained. The basal tegumentary region of the protoscolex consisted of irregularly-distributed, knoblike processes that were variable in size and shape, and contained an electron-dense cap. The IMP on the P face of the knoblike processes measured approximately the same diameter as those on the P face of the microthrix base. However, their density was about half that of the latter. The density of IMP on the E face of the knoblike processes could not be determined from the freeze-etch replicas.

Freeze-etch characterization of the teguments of three metacestodes: Echinococcus granulosus, Taenia crassiceps, and Taenia taeniaeformis.

The objective of this study was to characterize the teguments of metacestodes of Echinococcus granulosus, Taenia crassiceps, and Taenia taeniaeformis using the freeze-etch technique. Metacestodes of E. granulosus (19 mo old), T. crassiceps (28 days old), and T. taeniaeformis (34 days old) from gerbils, mice and rats, respectively, were fixed for 2 hr in 3% glutaraldehyde and then prepared for freeze-etching and thin sectioning by standard techniques. Freeze-etch replicas of the teguments of all three species displayed morphologic characteristics that were generally in agreement with previous ultrastructural work, although some new features and interpretations arose from use of this technique. For each species there was a concentric ring structure within the microthrix base, and cytoplasmic extensions of the perikarya into the distal tegument were membrane-bound rather than confluent bridges; these extensions frequently branched within the tegument. In addition, channels running from the proximal tegumental membrane to, and opening at the distal surface of, the tegument were seen in thin sections.

Possible factors influencing distribution and prevalence of Echinococcus granulosus in Utah.

A descriptive epidemiologic study was designed to test an impression that infections of Echinococcus granulosus in dogs, sheep, and human beings were concentrated in central Utah, and to determine when and how the parasite was introduced into the state, which factors were involved in the distribution of the cestode, and which factors increased either a person's risk of infection of the number of people at risk. Data were secured by review of available records, interviews, questionnaires, and field observations. It was found that 37 of 39 infections in human beings, and seven of eight counties with endemic hydatid disease in dogs and sheep, are located in central Utah. Possible factors responsible for the increasing number of people at risk were use of local people as herders, the existence of community herds, and specific dog management practices. Determinants such as trailing sheep between seasonal pastures, association of sheepmen from several counties on winter range, and sheep marketing practices undoubtedly influence distribution of infections in dogs and sheep.

Efficacy of praziquantel against immature Echinococcus multilocularis in dogs and cats.

Efficacy of an injectable formulation of praziquantel (given IM at a dosage of 5 mg/kg of body weight) against immature Echinococcus multilocularis was studied in 18 experimentally infected dogs and 22 experimentally infected cats. There were no worms recovered at necropsy from any of the treated hosts. However, whereas E multilocularis worms were recovered from all nontreated control dogs (n = 9; min-max 15-1,840, mean 483), such tapeworms were recovered from only k6 of the 11 nontreated control cats (min-max 2-820; overall mean 123.4). The study demonstrates 100% clearance of E multilocularis by praziquantel in experimentally infected dogs and cats, and shows that cats are not as suitable as experimental hosts for this parasite as are dogs.