Finger doses due to68Ga-labelled pharmaceuticals in PET departments-results of a multi-centre pilot study.

INTRODUCTION: Although the use of68Ga has increased substantially in nuclear medicine over the last decade, there is limited information available on occupational exposure due to68Ga. The purpose of this study is to determine the occupational extremity exposure during the preparation, dispensing and administration of68Ga-labelled radiopharmaceuticals. METHOD: Workers in eight centres wore a ring dosimeter for all tasks involving68Ga-labelled radiopharmaceuticals for a minimum of one month. Additionally, the fingertip dose was monitored in two centres and the hand with the highest ring dose during68Ga procedures was also identified in one centre. RESULTS: The median normalised ring dose for68Ga procedures was found to be 0.25 mSv GBq-1(range 0.01-3.34). The normalised68Ga ring doses recorded in this study are similar to that found in the literature for18F. This study is consistent with previous findings that the highest extremity dose is found on the non-dominant hand. A limited sub study in two of the centres showed a median fingertip to base of the finger dose ratio of 4.3. Based on this median ratio, the extrapolated annual68Ga fingertip dose for 94% of the workers monitored in this study would be below Category B dose limit (150 mSv) and no worker would exceed Category A dose limit (500 mSv). CONCLUSION: When appropriate shielding and radiation protection practices are employed, the extremity dose due to68Ga is comparable to that of18F and is expected to be well below the regulatory limits for the majority of workers.

Local bone metabolism during the consolidation process of spinal interbody fusion.

INTRODUCTION: Although computed tomography (CT) can identify the presence of eventual bony bridges following lumbar interbody fusion (LIF) surgery, it does not provide information on the ongoing formation process of new bony structures. 18F sodium fluoride (18F-NaF) positron emission tomography (PET) could be used as complementary modality to add information on the bone metabolism at the fusion site. However, it remains unknown how bone metabolism in the operated segment changes early after surgery in uncompromised situations. This study aimed to quantify the changes in local bone metabolism during consolidation of LIF. MATERIALS AND METHODS: Six skeletally mature sheep underwent LIF surgery. 18F-NaF PET/CT scanning was performed 6 and 12 weeks postoperatively to quantify the bone volume and metabolism in the operated segment. Bone metabolism was expressed as a function of bone volume. RESULTS: Early in the fusion process, bone metabolism was increased at the endplates of the operated vertebrae. In a next phase, bone metabolism increased in the center of the interbody region, peaked, and declined to an equilibrium state. During the entire postoperative time period of 12 weeks, bone metabolism in the interbody region was higher than that of a reference site in the spinal column. CONCLUSION: Following LIF surgery, there is a rapid increase in bone metabolism at the vertebral endplates that develops towards the center of the interbody region. Knowing the local bone metabolism during uncompromised consolidation of spinal interbody fusion might enable identification of impaired bone formation early after LIF surgery using 18F-NaF PET/CT scanning.

TSH suppression aggravates arterial inflammation - an 18F-FDG PET study in thyroid carcinoma patients.

PURPOSE: We aimed to investigate the influence of both hypothyroidism and thyroid-stimulating hormone (TSH) suppression on vascular inflammation, as assessed with 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT). METHODS: Ten thyroid carcinoma patients underwent an 18F-FDG PET/CT during post-thyroidectomy hypothyroidism and during thyrotropin (TSH) suppression after 131I (radioiodine) ablation therapy. We analysed the 18F-FDG uptake in the carotids, aortic arch, ascending, descending, and abdominal aorta to investigate the effects of thyroid hormone status on arterial inflammation. Target-to-background ratios (TBRs) corrected for blood pool activity were established for all arterial territories. Results were further compared to euthyroid historic control subjects. RESULTS: In general, there was a trend towards higher vascular TBRs during TSH suppression than during hypothyroidism (TBRmax all vessels = 1.6 and 1.8, respectively, p = 0.058), suggesting a higher degree of arterial inflammation. In concurrence with this, we found increased C-reactive protein (CRP) levels after levothyroxine treatment (CRP = 2.9 mg/l and 4.8 mg/l, p = 0.005). An exploratory comparison with euthyroid controls showed significant higher TBRs during TSH suppression for the carotids, aortic arch, thoracic descending aorta, and when all vascular territories were combined (TBRmaxp = 0.013, p = 0.016, p = 0.030 and p = 0.018 respectively). CONCLUSIONS: Arterial inflammation is increased during TSH suppression. This finding sheds new light on the underlying mechanism of the suspected increased risk of cardiovascular disease in patients with TSH suppression.

Glucose uptake in human brown adipose tissue is impaired upon fasting-induced insulin resistance.

AIMS/HYPOTHESIS: Human brown adipose tissue (BAT) has recently emerged as a potential target in the treatment of type 2 diabetes, owing to its capacity to actively clear glucose from the circulation­at least upon cold exposure. The effects of insulin resistance on the capacity of human BAT to take up glucose are unknown. Prolonged fasting is known to induce insulin resistance in peripheral tissues in order to spare glucose for the brain. METHODS: We studied the effect of fasting-induced insulin resistance on the capacity of BAT to take up glucose during cold exposure as well as on cold-stimulated thermogenesis. BAT glucose uptake was assessed by means of cold-stimulated dynamic 2-deoxy-2-[(18)F]fluoro-D-glucose positron emission tomography/computed tomography ([(18)F]FDG-PET/CT) imaging. RESULTS: We show that a 54 h fasting period markedly decreases both cold-induced BAT glucose uptake and nonshivering thermogenesis (NST) during cold stimulation. In vivo molecular imaging and modelling revealed that the reduction of glucose uptake in BAT was due to impaired cellular glucose uptake and not due to decreased supply. Interestingly, decreased BAT glucose uptake upon fasting was related to a decrease in core temperature during cold exposure, pointing towards a role for BAT in maintaining normothermia in humans. CONCLUSIONS/INTERPRETATION: Cold-stimulated glucose uptake in BAT is strongly reduced upon prolonged fasting. When cold-stimulated glucose uptake in BAT is also reduced under other insulin-resistant states, such as diabetes, cold-induced activation of BAT may not be a valid way to improve glucose clearance by BAT under such conditions. TRIAL REGISTRATION: www.trialregister.nl NTR3523 FUNDING: This work was supported by the EU FP7 project DIABAT (HEALTH-F2-2011-278373 to WDvML) and by the Netherlands Organization for Scientific Research (TOP 91209037 to WDvML).

Pseudarthrosis after lumbar spinal fusion: the role of ¹8F-fluoride PET/CT.

PURPOSE: Painful pseudarthrosis is one of the most important indications for (revision) surgery after spinal fusion procedures. If pseudarthrosis is the source of recurrent pain it may require revision surgery. It is therefore of great clinical importance to ascertain if it is the source of such pain. The correlation between findings on conventional imaging (plain radiography and CT) and clinical well-being has been shown to be moderate. The goal of this study was to determine the possible role of (18)F-fluoride PET in patients after lumbar spinal interbody fusion by investigating the relationship between PET/CT findings and clinical function and pain. METHODS: A cohort of 36 patients was retrospectively included in the study after (18)F-fluoride PET/CT for either persistent or recurrent low back pain (18 patients) or during routine postoperative investigation (18 patients) between 9 and 76 months and 11 and 14 months after posterior lumbar interbody fusion, respectively. Sixty minutes after intravenous injection of 156 - 263 MBq (mean 199 MBq, median 196 MBq) (18)F-fluoride, PET and CT images were acquired using an integrated PET/CT scanner, followed by a diagnostic CT scan. Two observers independently scored the images. The number of bony bridges between vertebrae was scored on the CT images to quantify interbody fusion (0, 1 or 2). Vertebral endplate and intervertebral disc space uptake were evaluated visually as well as semiquantitatively following (18)F-fluoride PET. Findings on PET and CT were correlated with clinical wellbeing as measured by validated questionnaires concerning general daily functioning (Oswestry Disability Index), pain (visual analogue scale) and general health status (EuroQol). Patients were divided into three categories based on these questionnaire scores. RESULTS: No correlation was found between symptom severity and fusion status. However, (18)F-fluoride activity in the vertebral endplates was significantly higher in patients in the lowest Oswestry Disability Index category (i.e. with the worst clinical performance) than in patients in higher categories (p = 0.01 between categories 1 and 2 and 1 and 3). The visual analogue scale and EuroQol results were similar although less pronounced, with only SUVmax between category 1 and 2 being significantly different (p = 0.04). CONCLUSION: We hypothesize that (18)F-fluoride PET/CT may be able to provide support for the diagnosis of painful pseudarthrosis and could serve as a tool to discriminate between symptomatic and asymptomatic pseudarthrosis for revision surgery, as CT defines the consolidation status and PET pinpoints the 'stress reaction' at the vertebral endplates which significantly correlates with Oswestry Disability Index score.

Cold-activated brown adipose tissue in human adults: methodological issues.

The relevance of functional brown adipose tissue (BAT) depots in human adults was undisputedly proven approximately seven years ago. Here we give an overview of all dedicated studies that were published on cold-induced BAT activity in adult humans that appeared since then. Different cooling protocols and imaging techniques to determine BAT activity are reviewed. BAT activation can be achieved by means of air- or water-cooling protocols. The most promising approach is individualized cooling, during which subjects are studied at the lowest temperature for nonshivering condition, probably revealing maximal nonshivering thermogenesis. The highest BAT prevalence (i.e., close to 100%) is observed using the individualized cooling protocol. Currently, the most widely used technique to study the metabolic activity of BAT is deoxy-2-[18F]fluoro-d-glucose ([18F]FDG)-positron emission tomography/computed tomography (PET/CT) imaging. Dynamic imaging provides quantitative information about glucose uptake rates, whereas static imaging reflects overall BAT glucose uptake, localization, and distribution. In general, standardized uptake values (SUV) are used to quantify BAT activity. An accurate determination of total BAT volume is hampered by the limited spatial resolution of the PET image, leading to spillover. Different research groups use different SUV threshold values, which make it difficult to directly compare BAT activity levels between studies. Another issue is the comparison of [18F]FDG uptake in BAT with respect to other tissues or upon with baseline values. This comparison can be performed by using the "fixed volume" methodology. Finally, the potential use of other relatively noninvasive methods to quantify BAT, like magnetic resonance imaging or thermography, is discussed.

Molecular imaging of brown adipose tissue in health and disease.

PURPOSE: Brown adipose tissue (BAT) has transformed from an interfering tissue in oncological (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET) to an independent imaging research field. This review takes the perspective from the imaging methodology on which human BAT research has come to rely on heavily. METHODS: This review analyses relevant PubMed-indexed publications that discuss molecular imaging methods of BAT. In addition, reported links between BAT and human diseases such as obesity are discussed, and the possibilities for imaging in these fields are highlighted. Radiopharmaceuticals aiming at several different biological mechanisms of BAT are discussed and evaluated. RESULTS: Prospective, dedicated studies allow visualization of BAT function in a high percentage of human subjects. BAT dysfunction has been implicated in obesity, linked with diabetes and associated with cachexia and atherosclerosis. Presently, (18)F-FDG PET/CT is the most useful tool for evaluating therapies aiming at BAT activity. In addition to (18)F-FDG, other radiopharmaceuticals such as (99m)Tc-sestamibi, (123)I-metaiodobenzylguanidine (MIBG), (18)F-fluorodopa and (18)F-14(R,S)-[(18)F]fluoro-6-thia-heptadecanoic acid (FTHA) may have a potential for visualizing other aspects of BAT activity. MRI methods are under continuous development and provide the prospect of functional imaging without ionizing radiation. CONCLUSION: Molecular imaging of BAT can be used to quantitatively assess different aspects of BAT metabolic activity.

Performance evaluation of iterative PET reconstruction with resolution recovery incorporating Gallium-68 positron range correction.

BACKGROUND: The distance traveled by the positron before annihilation with an electron, the so-called positron range, negatively effects the positron emission tomography (PET) image quality for radionuclides emitting high-energy positrons such as Gallium-68 (68Ga). PURPOSE: In this study, the effect of a tissue-independent positron range correction for Gallium-68 (68Ga-PRC) was investigated based on phantom measurements. The effect of the 68Ga-PRC was also explored in four patients. METHODS: The positron range distribution profile of 68Ga in water was generated via Monte Carlo simulation. That profile was mapped to a spatially invariant 3D convolution kernel which was incorporated in the OSEM and Q.Clear reconstruction algorithms to perform the 68Ga-PRC. In addition, each reconstruction method included point spread function (PSF) modeling and time-of-flight information. For both Fluorine-18 (18F) and 68Ga, the NEMA IQ phantom was filled with a sphere-to-background ratio of 10:1 and scanned with the GE Discovery MI 5R PET/CT system. Standard non-positron range correction (PRC) reconstructions were performed for both radionuclides, while also PRC reconstructions were performed for 68Ga. Reconstructions parameters (OSEM: number of updates, Q.Clear: beta value) were adapted to achieve similar noise levels between the corresponding reconstructions. The effect of 68Ga-PRC was assessed for both OSEM and Q.Clear reconstructions and compared to non-PRC reconstructions for 68Ga and 18F in terms of image contrast, noise, recovery coefficient (RC), and spatial resolution. For the clinical validation, 68Ga-labeled prostate-specific membrane antigen (68Ga-PSMA) and 68Ga-DOTATOC PET scans were included of two patients each. For each PET scan, patients were injected with 1.5 MBq/kg of 68Ga-PSMA or 68Ga-DOTATOC and the contrast-to-noise ratio (CNR) was calculated and compared to the non-PRC reconstructions. RESULTS: For OSEM reconstructions, including the 68Ga-PRC improved the RC by 9.4% (3.7%-19.3%) and spatial resolution by 21.7% (4.6 mm vs. 3.6 mm) for similar noise levels. For Q.Clear reconstructions, 68Ga-PRC modeling improved the RC by 6.7% (2.8%-10.5%) and spatial resolution by 15.3% (5.9 mm vs. 5.0 mm) while obtaining similar noise levels. In the patient data, the use of 68Ga-PRC enhanced the CNR by 13.2%. CONCLUSIONS: Including 68Ga-PRC in the PET reconstruction enhanced the image quality of 68Ga PET data compared to the standard non-PRC reconstructions for similar noise levels. Limited patient results also supported this improvement.

Dose rate conversion coefficients for ocular contamination in nuclear medicine: A Monte Carlo simulation with experimental validation.

BACKGROUND: Since 2011, the International Commission on Radiological Protection (ICRP) has recommended an annual eye lens dose limit of 20 mSv for radiation workers, averaged over 5 years, with no year exceeding 50 mSv. However, limited research has been conducted on dose rate conversion coefficients (DCCs) for direct contamination of the eye. PURPOSE: This study aimed to accurately determine DCCs for the eye lens and cornea for ocular contamination with radionuclides used in nuclear medicine. METHODS: DCCs for 37 radionuclides used in nuclear medicine were determined using two different methods. Method 1 involved conducting Monte Carlo (MC) simulations of an ICRU cylinder to determine the absorbed dose at a depth of 3 mm resulting from a point source. The accuracy of this simulation approach was validated by experimental thermoluminescent dosimeter (TLD) measurements for 18F, 68Ga, 99mTc, and 177Lu. In method 2, average DCCs were calculated for the eye lens (complete and radiosensitive parts) and the cornea for both a point source and thin surface contamination centered on the cornea using MC simulations on the adult mesh-type reference computational phantom of the eye from the ICRP (MRCP). RESULTS: DCCs determined from TLD measurements showed excellent agreement (deviations: +1.4%, +4.7%, -3.1%, and -2.5% for 18F, 68Ga, 99mTc, and 177Lu, respectively) compared to MC simulations of the experimental set-up. For the 37 radionuclides, DCCs of the complete eye-lens for a point source ranged from 2.53 × 10-7 to 4.15 × 10-2 mGy MBq-1 s-1 for the adult MRCPs, being substantially smaller compared to DCCs determined via MC simulations of a ICRU cylinder. In general, point source and surface contamination showed comparable DCCs for the eye lens. Radionuclides emitting low-energy beta radiation or conversion electrons (e.g., 177Lu, 99mTc) showed low DCCs as the radiation does not penetrate to the depth of the eye lens, while radionuclides emitting high-energy beta radiation (e.g., 90Y) showed high DCCs. Overall, DCCs for the radiosensitive part of the eye lens were larger (up to a factor of 3) compared to the complete eye lens. DCCs for the cornea were larger than for the eye lens with a factor that strongly depended on the emitted radiation type. Especially alpha emitters (e.g., 211At, 223Ra) showed high DCCs for the cornea because of the short range of alpha radiation, leading to local maxima in the cornea and not reaching the eye lens. CONCLUSION: DCCs at a depth of 3 mm in an ICRU cylinder and adult MRCP DCCs for both the complete and sensitive parts of the eye lens and cornea were determined for 37 radionuclides having applications in nuclear medicine. These DCCs are highly useful in radiation safety assessments and radiation dose calculations in ocular contamination incidents.

Extended MRI-based PET motion correction for cardiac PET/MRI.

PURPOSE: A 2D image navigator (iNAV) based 3D whole-heart sequence has been used to perform MRI and PET non-rigid respiratory motion correction for hybrid PET/MRI. However, only the PET data acquired during the acquisition of the 3D whole-heart MRI is corrected for respiratory motion. This study introduces and evaluates an MRI-based respiratory motion correction method of the complete PET data. METHODS: Twelve oncology patients scheduled for an additional cardiac 18F-Fluorodeoxyglucose (18F-FDG) PET/MRI and 15 patients with coronary artery disease (CAD) scheduled for cardiac 18F-Choline (18F-FCH) PET/MRI were included. A 2D iNAV recorded the respiratory motion of the myocardium during the 3D whole-heart coronary MR angiography (CMRA) acquisition (~ 10 min). A respiratory belt was used to record the respiratory motion throughout the entire PET/MRI examination (~ 30-90 min). The simultaneously acquired iNAV and respiratory belt signal were used to divide the acquired PET data into 4 bins. The binning was then extended for the complete respiratory belt signal. Data acquired at each bin was reconstructed and combined using iNAV-based motion fields to create a respiratory motion-corrected PET image. Motion-corrected (MC) and non-motion-corrected (NMC) datasets were compared. Gating was also performed to correct cardiac motion. The SUVmax and TBRmax values were calculated for the myocardial wall or a vulnerable coronary plaque for the 18F-FDG and 18F-FCH datasets, respectively. RESULTS: A pair-wise comparison showed that the SUVmax and TBRmax values of the motion corrected (MC) datasets were significantly higher than those for the non-motion-corrected (NMC) datasets (8.2 ± 1.0 vs 7.5 ± 1.0, p < 0.01 and 1.9 ± 0.2 vs 1.2 ± 0.2, p < 0.01, respectively). In addition, the SUVmax and TBRmax of the motion corrected and gated (MC_G) reconstructions were also higher than that of the non-motion-corrected but gated (NMC_G) datasets, although for the TBRmax this difference was not statistically significant (9.6 ± 1.3 vs 9.1 ± 1.2, p = 0.02 and 2.6 ± 0.3 vs 2.4 ± 0.3, p = 0.16, respectively). The respiratory motion-correction did not lead to a change in the signal to noise ratio. CONCLUSION: The proposed respiratory motion correction method for hybrid PET/MRI improved the image quality of cardiovascular PET scans by increased SUVmax and TBRmax values while maintaining the signal-to-noise ratio. Trial registration METC162043 registered 01/03/2017.

The tissue-specific metabolic effects of the PPARα agonist ciprofibrate in insulin-resistant male individuals: a double-blind, randomized, placebo-controlled crossover study.

OBJECTIVE: Insulin resistance is characterized by ectopic fat accumulation leading to cardiac diastolic dysfunction and nonalcoholic fatty liver disease. The objective of this study was to determine whether treatment with the peroxisome proliferator-activated receptor-α (PPARα) agonist ciprofibrate has direct effects on cardiac and hepatic metabolism and can improve insulin sensitivity and cardiac function in insulin-resistant volunteers. METHODS: Ten insulin-resistant male volunteers received 100 mg/d of ciprofibrate and placebo for 5 weeks in a randomized double-blind crossover study. Insulin-stimulated metabolic rate of glucose (MRgluc) was measured using dynamic 18 F-fluorodeoxyglucose-positron emission tomography (18 F-FDG-PET). Additionally, cardiac function, whole-body insulin sensitivity, intrahepatic lipid content, skeletal muscle gene expression, 24-hour blood pressure, and substrate metabolism were measured. RESULTS: Whole-body insulin sensitivity, energy metabolism, and body composition were unchanged after ciprofibrate treatment. Ciprofibrate treatment decreased insulin-stimulated hepatic MRgluc and increased hepatic lipid content. Myocardial net MRgluc tended to decrease after ciprofibrate treatment, but ciprofibrate treatment had no effect on cardiac function and cardiac energy status. In addition, no changes in PPAR-related gene expression in muscle were found. CONCLUSIONS: Ciprofibrate treatment increased hepatic lipid accumulation and lowered MRgluc, without affecting whole-body insulin sensitivity. Furthermore, parameters of cardiac function or cardiac energy status were not altered upon ciprofibrate treatment.

Dosimetry in molecular nuclear therapy.

Advanced personalized dosimetry for molecular nuclear therapy has been shown to be feasible in clinical practice. At the same time instrumentation and dosimetric software are still evolving at a high pace. Procedures developed so far differ in approach and sophistication, and standard operating procedures necessary for accurate patient specific dosimetry do not yet exist. For this reason we restricted ourselves to reviewing the literature and highlighting relevant developments.

Positron Range Corrections and Denoising Techniques for Gallium-68 PET Imaging: A Literature Review.

Gallium-68 (68Ga) is characterized by relatively high positron energy compared to Fluorine-18 (18F), causing substantial image quality degradation. Furthermore, the presence of statistical noise can further degrade image quality. The aim of this literature review is to identify the recently developed positron range correction techniques for 68Ga, as well as noise reduction methods to enhance the image quality of low count 68Ga PET imaging. The search engines PubMed and Scopus were employed, and we limited our research to published results from January 2010 until 1 August 2022. Positron range correction was achieved by using either deblurring or deep learning approaches. The proposed techniques improved the image quality and, in some cases, achieved an image quality comparable to 18F PET. However, none of these techniques was validated in clinical studies. PET denoising for 68Ga-labeled radiotracers was reported using either reconstruction-based techniques or deep learning approaches. It was demonstrated that both approaches can substantially enhance the image quality by reducing the noise levels of low count 68Ga PET imaging. The combination of 68Ga-specific positron range correction techniques and image denoising approaches may enable the application of low-count, high-quality 68Ga PET imaging in a clinical setting.

Evaluation of a Dedicated Radiofrequency Carotid PET/MRI Coil.

Carotid radiofrequency coils inside a PET/MRI system can result in PET quantification errors. We compared the performance of a dedicated PET/MRI carotid coil against a coil for MRI-only use. An 18F-fluorodeoxyglucose (18F-FDG) phantom was scanned without and with an MRI-only coil and with the PET/MRI coil. The decay-corrected normalized activity was compared for the different coil configurations. Eighteen patients were scanned with the three coil configurations. The maximal standardized uptake values (SUVmax) and signal-to-noise ratios (SNR) were calculated. Repeated measures ANOVA was performed to assess the differences in SUVmax and SNR between the coil configurations. In the phantom study, the PET/MRI coil demonstrated a slight decrease (<5%), while the MRI-only coil showed a substantial decrease (up to 10%) in normalized activity at the position of coil elements compared to no dedicated coil configuration. In the patient study, the SUVmax values for both no surface coil (3.59 ± 0.15) and PET/MRI coil (3.54 ± 0.15) were significantly higher (p = 0.03 and p = 0.04, respectively) as compared to the MRI-only coil (3.28 ± 0.16). No significant difference was observed between PET/MRI and no surface coil (p = 1.0). The SNR values for both PET/MRI (7.31 ± 0.44) and MRI-only (7.62 ± 0.42) configurations demonstrated significantly higher (p < 0.001) SNR values as compared to the no surface coil (3.78 ± 0.22), while no significant difference was observed in SNR between the PET/MRI and MRI-only coil (p = 1.0). This study demonstrated that the PET/MRI coil can be used for PET imaging without requiring attenuation correction while acquiring high-resolution MR images.

Brown adipose tissue activation is not related to hypermetabolism in emphysematous chronic obstructive pulmonary disease patients.

BACKGROUND: Brown adipose tissue (BAT) has been primarily researched as a potential target for mitigating obesity. However, the physiological significance of BAT in relation to cachexia remains poorly understood. The objective of this study was to investigate the putative contribution of BAT on different components of energy metabolism in emphysematous chronic obstructive pulmonary disease (COPD) patients. METHODS: Twenty COPD patients (mean ± SD age 62 ± 6, 50% female, median [range] BMI 22.4 [15.1-32.5] kg/m2 and 85% low FFMI) were studied. Basal metabolic rate (BMR) was assessed by ventilated hood, total daily energy expenditure (TDEE) by doubly labelled water and physical activity by triaxial accelerometry. BMR was adjusted for fat-free mass (FFM) as assessed by deuterium dilution. Analysis of BAT and WAT was conducted in a subset of ten patients and six age-matched, gender-matched and BMI-matched healthy controls. BAT glucose uptake was assessed by means of cold-stimulated integrated [18F]FDG positron-emission tomography and magnetic resonance imaging. WAT was collected from subcutaneous abdominal biopsies to analyse metabolic and inflammatory gene expression levels. Lung function was assessed by spirometry and body plethysmography and systemic inflammation by high sensitivity C-reactive protein. RESULTS: Mean TDEE was 2209 ± 394 kcal/day, and mean BMR was 1449 ± 214 kcal/day corresponding to 120% of predicted. FFM-adjusted BMR did not correlate with lung function or C-reactive protein. Upon cooling, energy expenditure increased, resulting in a non-shivering thermogenesis of (median [range]) 20.1% [3.3-41.3] in patients and controls. Mean BAT glucose uptake was comparable between COPD and controls (1.5 [0.1-6.2] vs. 1.1 [0.7-3.9]). In addition, no correlation was found between BMR adjusted for FFM and BAT activity or between cold-induced non-shivering energy expenditure and BAT activity. Gene expression levels of the brown adipocyte or beige markers were also comparable between the groups. No (serious) adverse events were reported. CONCLUSIONS: Although COPD patients were hypermetabolic at rest, no correlation was found between BMR or TDEE and BAT activity. Furthermore, both BAT activity and gene expression levels of the brown adipocyte or beige markers were comparable between COPD patients and controls.

An international multi-center investigation on the accuracy of radionuclide calibrators in nuclear medicine theragnostics.

BACKGROUND: Personalized molecular radiotherapy based on theragnostics requires accurate quantification of the amount of radiopharmaceutical activity administered to patients both in diagnostic and therapeutic applications. This international multi-center study aims to investigate the clinical measurement accuracy of radionuclide calibrators for 7 radionuclides used in theragnostics: 99mTc, 111In, 123I, 124I, 131I, 177Lu, and 90Y. METHODS: In total, 32 radionuclide calibrators from 8 hospitals located in the Netherlands, Belgium, and Germany were tested. For each radionuclide, a set of four samples comprising two clinical containers (10-mL glass vial and 3-mL syringe) with two filling volumes were measured. The reference value of each sample was determined by two certified radioactivity calibration centers (SCK CEN and JRC) using two secondary standard ionization chambers. The deviation in measured activity with respect to the reference value was determined for each radionuclide and each measurement geometry. In addition, the combined systematic deviation of activity measurements in a theragnostic setting was evaluated for 5 clinically relevant theragnostic pairs: 131I/123I, 131I/124I, 177Lu/111In, 90Y/99mTc, and 90Y/111In. RESULTS: For 99mTc, 131I, and 177Lu, a small minority of measurements were not within ± 5% range from the reference activity (percentage of measurements not within range: 99mTc, 6%; 131I, 14%; 177Lu, 24%) and almost none were outside ± 10% range. However, for 111In, 123I, 124I, and 90Y, more than half of all measurements were not accurate within ± 5% range (111In, 51%; 123I, 83%; 124I, 63%; 90Y, 61%) and not all were within ± 10% margin (111In, 22%; 123I, 35%; 124I, 15%; 90Y, 25%). A large variability in measurement accuracy was observed between radionuclide calibrator systems, type of sample container (vial vs syringe), and source-geometry calibration/correction settings used. Consequently, we observed large combined deviations (percentage deviation > ± 10%) for the investigated theragnostic pairs, in particular for 90Y/111In, 131I/123I, and 90Y/99mTc. CONCLUSIONS: Our study shows that substantial over- or underestimation of therapeutic patient doses is likely to occur in a theragnostic setting due to errors in the assessment of radioactivity with radionuclide calibrators. These findings underline the importance of thorough validation of radionuclide calibrator systems for each clinically relevant radionuclide and sample geometry.

A comparison of four radionuclide dose calibrators using various radionuclides and measurement geometries clinically used in nuclear medicine.

PURPOSE: Reliable quantification of radioactivity in nuclear medicine is becoming increasingly important in various therapeutic applications requiring a high accuracy of nuclear medicine measuring equipment, such as radionuclide calibrators. In this study the accuracy of four different radionuclide calibrators was assessed for 99mTc, 111In, 68Ga and 18F for measurement geometries clinically used. METHODS: Syringes and vials were prepared with a reference activity using a stock solution of which the activity concentration was determined using gamma-ray spectroscopy. The accuracy of four different radionuclide calibrator systems, ISOMED 2000, ISOMED 2010, VIK-202 and Capintec CRC-25R, was assessed by comparing the measured activity to the reference activity. RESULTS: Deviations in measured activity from reference values were found up to 12.5%, 32.0%, 29.0% and 12.6% for 99mTc, 111In, 68Ga and 18F, respectively. For 68Ga all radionuclide calibrators systematically overestimated the activity by 10-20%. For 111In, large differences in activity measurements were observed between different source geometries, in particular between syringes and vials. Deviations between radionuclide calibrator systems were found up to 11.8%, 44.4%, 14.4% and 8.7% for 99mTc, 111In, 68Ga and 18F, respectively. When comparing similar syringe types of different brands filled with identical stock solution volume, deviations up to 1.8%, 5.8%, 10.2% and 3.2% were found for 99mTc, 111In, 68Ga and 18F. CONCLUSION: Substantial deviations in measured activity were found for all radionuclides and radionuclide calibrators, which may result in erroneous activity dosing and image quantification. This underlines the importance of thorough validation of radionuclide calibrators for all measurement geometries and radionuclides clinically used.

Performing clinical 18F-FDG-PET/MRI of the mediastinum optimising a dedicated, patient-friendly protocol.

OBJECTIVE: To construct a mediastinal-specific fluorine-18-fluorodeoxyglucose (F-FDG)-PET/MR protocol with high-quality MRI of minimal acquisition-time and comparable diagnostic value to F-FDG-PET/computed tomography (CT). MATERIALS AND METHODS: Fifteen healthy participants received PET/MRI and 10 patients with mediastinal tumours (eight non-small-cell lung, two oesophageal cancer) received F-FDG-PET/MRI immediately after F-FDG-PET/CT. Sequences volume interpolated breath-hold examination (T1-VIBE) and Half-Fourier acquisition single-shot turbo spin echo (T2-HASTE) were optimised by varying the parameters: breath-hold (BH, end-expiration), fat suppression (spectral adiabatic inversion recovery), and ECG-triggering (ECG, end-diastole). Image quality (IQ) of each sequence-variation was qualitatively scored by medical experts and quantitatively assessed by calculating signal-to-noise ratios, contrast relative to muscle, standardized-uptake-value, and tumour-to-blood ratios. Patient comfort was evaluated on patients' experience. Diagnostic accuracy of F-FDG-PET/MRI was compared to F-FDG-PET/CT, in reference to histopathology/cytopathology. RESULTS: ECG-triggered T1-VIBE images showed the highest signal-to-noise ratio (P < 0.01) and the largest contrast between mediastinal soft-tissues, regardless of BH or free-breathing acquisition. IQ of ECG-triggered T1-VIBE scans in BH were scored qualitatively highest with good reader agreement (κ = 0.62). IQ of T2-HASTE was not significantly affected by BH acquisition (P > 0.9). Qualitative IQ of T1-VIBE and T2-HASTE declined after spectral adiabatic inversion recovery fat-suppression. All patients could maintain BH at end-expiration and reported no discomfort. Diagnostic performance of F-FDG-PET/MR was not significantly different from F-FDG-PET/CT with comparable staging, standardized-uptake-values, and tumour-to-blood ratios. However, T-status was more often over-staged on F-FDG-PET/CT, while N-status was more frequently under-staged on F-FDG-PET/MR. CONCLUSION: ECG-triggered T1-VIBE sequences acquired during short, multiple BHs are recommended for mediastinal imaging using F-FDG-PET/MR. With dedicated protocols, F-FDG-PET/MRI will be useful in thoracic oncology and aid in diagnostic evaluation and tailored treatment decision-making.

Towards standardization of absolute SPECT/CT quantification: a multi-center and multi-vendor phantom study.

Absolute quantification of radiotracer distribution using SPECT/CT imaging is of great importance for dosimetry aimed at personalized radionuclide precision treatment. However, its accuracy depends on many factors. Using phantom measurements, this multi-vendor and multi-center study evaluates the quantitative accuracy and inter-system variability of various SPECT/CT systems as well as the effect of patient size, processing software and reconstruction algorithms on recovery coefficients (RC). METHODS: Five SPECT/CT systems were included: Discovery™ NM/CT 670 Pro (GE Healthcare), Precedence™ 6 (Philips Healthcare), Symbia Intevo™, and Symbia™ T16 (twice) (Siemens Healthineers). Three phantoms were used based on the NEMA IEC body phantom without lung insert simulating body mass indexes (BMI) of 25, 28, and 47 kg/m2. Six spheres (0.5-26.5 mL) and background were filled with 0.1 and 0.01 MBq/mL 99mTc-pertechnetate, respectively. Volumes of interest (VOI) of spheres were obtained by a region growing technique using a 50% threshold of the maximum voxel value corrected for background activity. RC, defined as imaged activity concentration divided by actual activity concentration, were determined for maximum (RCmax) and mean voxel value (RCmean) in the VOI for each sphere diameter. Inter-system variability was expressed as median absolute deviation (MAD) of RC. Acquisition settings were standardized. Images were reconstructed using vendor-specific 3D iterative reconstruction algorithms with institute-specific settings used in clinical practice and processed using a standardized, in-house developed processing tool based on the SimpleITK framework. Additionally, all data were reconstructed with a vendor-neutral reconstruction algorithm (Hybrid Recon™; Hermes Medical Solutions). RESULTS: RC decreased with decreasing sphere diameter for each system. Inter-system variability (MAD) was 16 and 17% for RCmean and RCmax, respectively. Standardized reconstruction decreased this variability to 4 and 5%. High BMI hampers quantification of small lesions (< 10 ml). CONCLUSION: Absolute SPECT quantification in a multi-center and multi-vendor setting is feasible, especially when reconstruction protocols are standardized, paving the way for a standard for absolute quantitative SPECT.

Short-term discontinuation of vagal nerve stimulation alters 18F-FDG blood pool activity: an exploratory interventional study in epilepsy patients.

BACKGROUND: Vagus nerve activation impacts inflammation. Therefore, we hypothesized that vagal nerve stimulation (VNS) influenced arterial wall inflammation as measured by 18F-FDG uptake. RESULTS: Ten patients with left-sided VNS for refractory epilepsy were studied during stimulation (VNS-on) and in the hours after stimulation was switched off (VNS-off). In nine patients, 18F-FDG uptake was measured in the right carotid artery, aorta, bone marrow, spleen, and adipose tissue. Target-to-background ratios (TBRs) were calculated to normalize the respective standardized uptake values (SUVs) for venous blood pool activity. Median values are shown with interquartile range and compared using the Wilcoxon signed-rank test. Arterial SUVs tended to be higher during VNS-off than VNS-on [SUVmax all vessels 1.8 (1.5-2.2) vs. 1.7 (1.2-2.0), p = 0.051]. However, a larger difference was found for the venous blood pool at this time point, reaching statistical significance in the vena cava superior [meanSUVmean 1.3 (1.1-1.4) vs. 1.0 (0.8-1.1); p = 0.011], resulting in non-significant lower arterial TBRs during VNS-off than VNS-on. Differences in the remaining tissues were not significant. Insulin levels increased after VNS was switched off [55.0 pmol/L (45.9-96.8) vs. 48.1 pmol/L (36.9-61.8); p = 0.047]. The concurrent increase in glucose levels was not statistically significant [4.8 mmol/L (4.7-5.3) vs. 4.6 mmol/L (4.5-5.2); p = 0.075]. CONCLUSIONS: Short-term discontinuation of VNS did not show a consistent change in arterial wall 18F-FDG-uptake. However, VNS did alter insulin and 18F-FDG blood levels, possibly as a result of sympathetic activation.