Clinical significance of subcutaneous fat and fascial involvement in juvenile dermatomyositis.

Objectives: Subcutaneous involvement, including calcinosis and panniculitis, is a more common complication in juvenile dermatomyositis (JDM) than in adult dermatomyositis. Magnetic resonance imaging (MRI) is useful for evaluating disease distribution. We investigated the clinical significance of subcutaneous involvement in JDM. Methods: Thighs and hips in 18 newly diagnosed JDM patients were evaluated with fat-suppression MRI. Bilateral muscle, fascial and subcutaneous fat involvement were scored from 0 to 8 points according to the severity of distribution on MRI. Associations between clinical manifestations, serum muscle enzymes, and MRI scores were also evaluated. Results: Abnormal MRI findings in muscle, fascia and subcutaneous fat were observed in 18, 18, and 10 patients, respectively. Subcutaneous fat scores were significantly higher in early-diagnosed JDM patients (diagnosed less than 2 months from onset) than in late-diagnosed JDM patients (diagnosed later) (p = .025). Serum aldolase was elevated in all patients, although only eight demonstrated elevated serum creatine phosphokinase. Serum aldolase was significantly correlated with MRI scores for subcutaneous fat (p < .0001, ρ = .787) and fascia (p = .013 ρ = 0.574), but not muscle. Additionally, serum aldolase was significantly correlated with serum triglycerides (p = .009, ρ = 0.629). Conclusion: Subcutaneous fat involvement is a characteristic finding in early-diagnosed JDM and correlates with elevated serum aldolase.

Prognostic implications of 62Cu-diacetyl-bis (N4-methylthiosemicarbazone) PET/CT in patients with glioma.

OBJECTIVE: The potential of positron emission tomography/computed tomography using 62Cu-diacetyl-bis (N4-methylthiosemicarbazone) (62Cu-ATSM PET/CT), which was originally developed as a hypoxic tracer, to predict therapeutic resistance and prognosis has been reported in various cancers. Our purpose was to investigate prognostic value of 62Cu-ATSM PET/CT in patients with glioma, compared to PET/CT using 2-deoxy-2-[18F]fluoro-D-glucose (18F-FDG). METHOD: 56 patients with glioma of World Health Organization grade 2-4 were enrolled. All participants had undergone both 62Cu-ATSM PET/CT and 18F-FDG PET/CT within mean 33.5 days prior to treatment. Maximum standardized uptake value and tumor/background ratio were calculated within areas of increased radiotracer uptake. The prognostic significance for progression-free survival and overall survival were assessed by log-rank test and Cox's proportional hazards model. RESULTS: Disease progression and death were confirmed in 37 and 27 patients in follow-up periods, respectively. In univariate analysis, there was significant difference of both progression-free survival and overall survival in age, tumor grade, history of chemoradiotherapy, maximum standardized uptake value and tumor/background ratio calculated using 62Cu-ATSM PET/CT. Multivariate analysis revealed that maximum standardized uptake value calculated using 62Cu-ATSM PET/CT was an independent predictor of both progression-free survival and overall survival (p < 0.05). In a subgroup analysis including patients of grade 4 glioma, only the maximum standardized uptake values calculated using 62Cu-ATSM PET/CT showed significant difference of progression-free survival (p < 0.05). CONCLUSIONS: 62Cu-ATSM PET/CT is a more promising imaging method to predict prognosis of patients with glioma compared to 18F-FDG PET/CT.

Use of count-based image reconstruction to evaluate the variability and repeatability of measured standardised uptake values.

Standardized uptake values (SUVs) are the most widely used quantitative imaging biomarkers in PET. It is important to evaluate the variability and repeatability of measured SUVs. Phantom studies seem to be essential for this purpose; however, repetitive phantom scanning is not recommended due to the decay of radioactivity. In this study, we performed count-based image reconstruction to avoid the influence of decay using two different PET/CT scanners. By adjusting the ratio of 18F-fluorodeoxyglucose solution to tap water, a NEMA IEC body phantom was set for SUVs of 4.0 inside six hot spheres. The PET data were obtained using two scanners (Aquiduo and Celesteion; Toshiba Medical Systems, Tochigi, Japan). We set the start time for image reconstruction when the total radioactivity in the phantom was 2.53 kBq/cc, and employed the counts of the first 2-min acquisition as the standard. To maintain the number of counts for each image, we set the acquisition time for image reconstruction depending on the decay of radioactivity. We obtained 50 images, and calculated the SUVmax and SUVpeak of all six spheres in each image. The average values of the SUVmax were used to calculate the recovery coefficients to compare those measured by the two different scanners. Bland-Altman analyses of the SUVs measured by the two scanners were also performed. The measured SUVs using the two scanners exhibited a 10-30% difference, and the standard deviation (SD) of the measured SUVs was between 0.1-0.2. The Celesteion always exhibited higher values than the Aquiduo. The smaller sphere exhibited a larger SD, and the SUVpeak had a smaller SD than the SUVmax. The Bland-Altman analyses showed poor agreement between the SUVs measured by the two scanners. The recovery coefficient curves obtained from the two scanners were considerably different. The Celesteion exhibited higher recovery coefficients than the Aquiduo, especially at approximately 20-mm-diameter. Additionally, the curves were lower than those calculated from the standard 30-min acquisition images. We propound count-based image reconstruction to evaluate the variability and repeatability of measured SUVs. These results are also applicable for the standardization and harmonization of SUVs in multi-institutional studies.

Variation and repeatability of measured standardized uptake values depending on actual values: a phantom study.

Standardized uptake values (SUVs) are the most widely used quantitative imaging biomarkers in positron emission tomography (PET); however, little is known about the changes in variation and repeatability of SUVs depending on the magnitude of the values. We hypothesized that low SUVs have larger variations than high SUVs, and attempted various kinds of experimental PET scans using a phantom. By adjusting the ratio of F-18 solution to tap water, a NEMA IEC body phantom was set for SUVs of 2.0, 4.0, and 8.0 inside six hot spheres. PET data were obtained for 4 hours, and the data reconstructed every 2 min. The SUVmax and SUVpeak of the spheres in all images were recorded. The relative SUVs were calculated by dividing the measured SUV by actual SUV, and used for the Bland-Altman plots. Some variation was observed for the measured SUVs. The measured SUVs for the actual SUV of 2.0 showed the largest variation among those of 2.0, 4.0, and 8.0, and those of 8.0 showed the smallest. Similarly, the relative SUVs showed significantly larger variations for lower values. In addition, the relative SUVmax showed larger variation and value than the relative SUVpeak. The Bland-Altman plots showed considerable variation and little agreement, but the degree of variation decreased as the measured value increased. We demonstrated some variation of the measured SUVs, which decreased for larger measured values. Clinicians should consider the inaccuracy of low SUVs not only in daily practice, but also for multi-institutional studies.

Initial evaluation of the Celesteion large-bore PET/CT scanner in accordance with the NEMA NU2-2012 standard and the Japanese guideline for oncology FDG PET/CT data acquisition protocol version 2.0.

BACKGROUND: The goal of this study was to evaluate the performance of the Celesteion positron emission tomography/computed tomography (PET/CT) scanner, which is characterized by a large-bore and time-of-flight (TOF) function, in accordance with the NEMA NU-2 2012 standard and version 2.0 of the Japanese guideline for oncology fluorodeoxyglucose PET/CT data acquisition protocol. Spatial resolution, sensitivity, count rate characteristic, scatter fraction, energy resolution, TOF timing resolution, and image quality were evaluated according to the NEMA NU-2 2012 standard. Phantom experiments were performed using 18F-solution and an IEC body phantom of the type described in the NEMA NU-2 2012 standard. The minimum scanning time required for the detection of a 10-mm hot sphere with a 4:1 target-to-background ratio, the phantom noise equivalent count (NECphantom), % background variability (N 10mm), % contrast (Q H,10mm), and recovery coefficient (RC) were calculated according to the Japanese guideline. RESULTS: The measured spatial resolution ranged from 4.5- to 5-mm full width at half maximum (FWHM). The sensitivity and scatter fraction were 3.8 cps/kBq and 37.3%, respectively. The peak noise-equivalent count rate was 70 kcps in the presence of 29.6 kBq mL-1 in the phantom. The system energy resolution was 12.4% and the TOF timing resolution was 411 ps at FWHM. Minimum scanning times of 2, 7, 6, and 2 min per bed position, respectively, are recommended for visual score, noise-equivalent count (NEC)phantom, N 10mm, and the Q H,10mm to N 10mm ratio (QNR) by the Japanese guideline. The RC of a 10-mm-diameter sphere was 0.49, which exceeded the minimum recommended value. CONCLUSIONS: The Celesteion large-bore PET/CT system had low sensitivity and NEC, but good spatial and time resolution when compared to other PET/CT scanners. The QNR met the recommended values of the Japanese guideline even at 2 min. The Celesteion is therefore thought to provide acceptable image quality with 2 min/bed position acquisition, which is the most common scan protocol in Japan.

Quantification of temporal changes in calcium score in active atherosclerotic plaque in major vessels by 18F-sodium fluoride PET/CT.

PURPOSE: Our aim was to assess whether 18F-NaF PET/CT is able to predict progression of the CT calcium score. METHODS: Between August 2007 and November 2015, 34 patients (18 women, 16 men; age, mean ± standard deviation, 57.5 ± 13.9 years; age range 19-78 years) with malignancy or orthopaedic disease were enrolled in this study, with approximately 1-year follow-up data. Baseline and follow-up CT images were retrospectively evaluated for the presence of calcification sites in major vessel walls. The maximum and mean CT values (CTmax and CTmean, in Hounsfield units), calcification volumetric score (CVS, in cubic millimetres) and Agatston units score (AU) were evaluated for each site. Subsequent changes in CTmax, CTmean, CVS and AU were calculated and expressed as ΔCTmax, ΔCTmean, ΔCVS and ΔAU, respectively. We then evaluated the relationship between 18F-NaF uptake (using the maximum target-to-background ratio, TBRmax, and the maximum blood-subtracted 18F-NaF activity, bsNaFmax, which was obtained by subtracting the SUVmax of each calcified plaque lesion and NaF-avid site from the SUVmean in the right atrium blood pool) and the change in calcified plaque volume and characteristics obtained after 1 year. RESULTS: We detected and analysed 182 calcified plaque sites and 96 hot spots on major vessel walls. 18F-NaF uptake showed very weak correlations with CTmax, CTmean, CVS, CVS after 1 year, AU and AU after 1 year on both baseline and follow-up PET/CT scans for each site. 18F-NaF uptake showed no correlation with ΔCTmax or ΔCTmean. However, there was a significant correlation between the intensity of 18F-NaF uptake and ΔCVS and ΔAU. CONCLUSION: 18F-NaF uptake has a strong correlation with calcium score progression which was a predictor of future cardiovascular disease risk. PET/CT using 18F-NaF may be able to predict calcium score progression which is known to be the major characteristic of atherosclerosis.

Multimodal approach to detect osseous involvement in meningioma: additional value of (18)F-fluoride PET/CT for conventional imaging.

PURPOSE: To compare the diagnostic performance of fluorine 18 ((18)F) fluoride positron emission tomography (PET)/computed tomography (CT) with that of conventional imaging (CT and magnetic resonance [MR] imaging) in evaluating the osseous involvement in meningioma. MATERIALS AND METHODS: The study was approved by the ethics committee and institutional review board and was conducted according to the Declarations of Helsinki and Tokyo. Written informed consent was obtained from all patients. A retrospective comparative study between (18)F-fluoride PET/CT and conventional imaging was conducted to detect osseous involvement in patients with a verified diagnosis of meningioma. Osseous involvement was verified by using definitive surgery (including drilling or careful sampling of the skull in all patients). The diagnostic performance, determined by calculating the sensitivity, specificity, positive predictive value ( PPV positive predictive value ), negative predictive value ( NPV negative predictive value ), and accuracy, was assessed. RESULTS: Data sets from a total of 78 patients with proven meningioma were compared. Osseous involvement was histopathologically confirmed in 25 patients (32%). The sensitivity, specificity, PPV positive predictive value , NPV negative predictive value , and accuracy were 92.0%, 86.8%, 76.7%, 95.8%, and 88.5% for (18)F-fluoride PET/CT and 64.0%, 83.0%, 64.0%, 83.0%, and 76.9% for conventional imaging, respectively. The receiver operating characteristic ( ROC receiver operating characteristic ) analysis revealed that the area under the ROC receiver operating characteristic curve ( Az area under the ROC curve ) value of (18)F-fluoride PET/CT was significantly greater than that of conventional imaging (0.965 ± 0.02 [standard error] vs 0.703 ± 0.066 [standard error], P < .0001). CONCLUSION: An approach using (18)F-fluoride PET/CT improves preoperative detection of osseous involvement. In those without abnormal (18)F-fluoride uptake within the skull, the patient may proceed directly to conventional surgery. However, a positive finding of osseous involvement at (18)F-fluoride PET/CT should prompt confirmation by drilling or sampling of bone.

Tumor hypoxia and microscopic diffusion capacity in brain tumors: a comparison of (62)Cu-Diacetyl-Bis (N4-Methylthiosemicarbazone) PET/CT and diffusion-weighted MR imaging.

OBJECTIVES: The aim of this study was to clarify the relationship between tumor hypoxia and microscopic diffusion capacity in primary brain tumors using (62)Cu-Diacetyl-Bis (N4-Methylthiosemicarbazone) ((62)Cu-ATSM) PET/CT and diffusion-weighted MR imaging (DWI). METHODS: This study was approved by the institutional human research committee and was HIPAA compliant, and informed consent was obtained from all patients. (62)Cu-ATSM PET/CT and DWI were performed in a total of 40 primary brain tumors of 34 patients with low grade glioma (LGG, n = 13), glioblastoma (GBM, n = 20), and primary central nervous system lymphoma (PCNSL, n = 7). (62)Cu-ATSM PET/CT parameters and apparent diffusion coefficient (ADC) obtained by DWI were compared. RESULTS: High intensity signals by (62)Cu-ATSM PET/CT and DWI in patients with GBM and PCNSL, and low intensity signals in LGG patients were observed. An inverse correlation was found between maximum SUV (SUVmax) and minimum ADC (ADCmin) (r = -0.583, p < 0.0001), and between tumor/brain ratio (T/Bratio) and ADCmin for all tumors (r = -0.532, p < 0.0001). Both SUVmax and T/Bratio in GBM were higher than LGG (p < 0.0001 and p < 0.0001), and those in PCNSL were also higher than GBM (p = 0.033 and p = 0.044). The ADCmin was lower in GBM (p = 0.011) and PCNSL (p = 0.01) than in LGG, while no significant difference was found between GBM and PCNSL (p = 0.90). CONCLUSION: Tumor hypoxia assessed by (62)Cu-ATSM PET/CT correlated with microscopic diffusion capacity obtained by DWI in brain tumors. Both (62)Cu-ATSM PET/CT and DWI were considered feasible imaging methods for grading glioma. However, (62)Cu-ATSM PET/CT provided additional diagnostic information to differentiate between GBM and PCNSL.

Biodistribution and radiation dosimetry of [¹8F]-5-fluorouracil.

PURPOSE: To estimate the radiation dose and biodistribution of (18)F-5-fluorouracil ([(18)F]-5-FU) from positron emission tomography/computed tomography (PET/CT) data, and to extrapolate mouse data to human data in order to evaluate cross-species consistency. METHODS: Fifteen cancer patients (head and neck cancer (n=11), colon cancer (n=4)) were enrolled. Sequential PET/CT images were acquired for 2h after intravenous administration of [(18)F]-5-FU, and the percent of the injected dose delivered to each organ was derived. For comparison, [(18)F]-5-FU was administered to female BALB/cAJcl-nu/nu nude mice (n=19), and the percent of the injected dose delivered to mouse organs was extrapolated to the human model. Absorbed radiation dose was calculated using OLINDA/EXM 1.0 software. RESULTS: In human subjects, high [(18)F]-5-FU uptake was seen in the liver, gallbladder and kidneys. The absorbed dose was highest in the gallbladder wall. In mice, the biodistribution of [(18)F]-5-FU corresponded to that of humans. Estimated absorbed radiation doses for all organs were moderately correlated, and doses to organs (except the gallbladder and urinary bladder) were significantly correlated between mice and humans. The mean effective [(18)F]-5-FU dose was higher in humans (0.0124mSv/MBq) than in mice (0.0058mSv/MBq). CONCLUSION: Biodistribution and radiation dosimetry of [(18)F]-5-FU were compared between humans and mice: biodistribution in mice and humans was similar. Data from mice underestimated the effective dose in humans, suggesting that clinical measurements are needed for more detailed dose estimation in order to ensure radiation safety. The observed effective doses suggest the feasibility of [(18)F]-5-FU PET/CT for human studies.

Periventricular nodular heterotopia is related to severity of the hindbrain deformity in Chiari II malformation.

BACKGROUND: Knowledge of the occurrence of malformations of cortical development (MCDs) and its relationship to hindbrain deformity in Chiari II malformation (CIIM) is limited. OBJECTIVE: To assess malformations of cortical development and its relationship to hindbrain deformity regarding Chiari II malformation. MATERIALS AND METHODS: Brain and cervical spinal MRI from 66 children (age range, 1-256 days; mean age, 22.3 days) with Chiari II malformation were retrospectively reviewed. If present, the type, number and location of malformations of cortical development were recorded. Hindbrain deformity was assessed for the level of the medullary kink, the descent of the pons and the shape of the fourth ventricle; these parameters were compared in children with and without malformations of cortical development. RESULTS: Twenty children with malformations of cortical development were identified. Only periventricular nodular heterotopia was noted. The median level of the medullary kink was significantly lower in children with malformations of cortical development compared with children without it (P = 0.037). A low pontomesencephalic junction was identified more frequently in children with malformations of cortical development (65.0%), relative to children without malformations of cortical development (34.8%) (P = 0.045). The fourth ventricular shape was not significantly different in children with or without malformations of cortical development (P = 0.684). CONCLUSION: Periventricular nodular heterotopia was seen in a relatively high proportion of children with Chiari II malformation, suggesting that it may be associated with severe hindbrain deformity.