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.

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.

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.

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.

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.

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.

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.

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.

Impact of prompt gamma coincidence correction on absorbed dose estimation in differentiated thyroid cancer using 124I PET/CT imaging.

INTRODUCTION: Iodine-124 positron emission tomography/computed tomography (I PET/CT) is increasingly being used in the absorbed dose estimation in the radioiodine treatment of differentiated thyroid cancer (DTC). However, the produced prompt gamma coincidences (PGCs) associated with the I decay result in a bias in the absorbed dose estimation. The impact of a sinogram-based PGC correction approach on the absorbed dose estimation in I PET/CT DTC imaging is investigated. METHODS: I phantom and patient measurements were performed on a Siemens Biograph mCT PET/CT system. All images were reconstructed with (PGCon) and without PGC correction (PGCoff). The phantom contained seven spheres (diameters: 6.6-37 mm). The spheres and background compartment were filled with a I solution, resulting in a low (9.4 : 1) and a high sphere-to-background activity concentration ratio (750 : 1). Sphere recovery coefficient (RC) values were determined. In addition, the impact of PGC correction on measured lesion uptake and calculated lesion-absorbed dose was assessed for 66 lesions identified in 24 DTC patients. RESULTS: PGC correction systematically increased sphere RC values up to 71% for the smallest spheres. For the patient data, PGC correction significantly increased both the measured I uptake (P<0.005) and the calculated lesion-absorbed dose (P=0.008) by ∼3%. The percentage difference in the calculated lesion-absorbed dose ranged from -19% to 50%, showing that PGC correction had a variable and large impact for a few lesions. CONCLUSION: PGC correction resulted in significantly higher sphere RC values, I lesion uptake values and estimated lesion-absorbed doses.

Thyroid Gland 18F-FDG Uptake in Neurofibromatosis Type 1.

PURPOSE: To investigate thyroid gland characteristics on 18F-FDG positron emission tomography/computed tomography (PET/CT) imaging in patients with neurofibromatosis type 1 (NF1). SUBJECTS AND METHODS: Thyroid gland characteristics of patients with a clinical diagnosis of NF1 who underwent 18F-FDG PET/CT imaging for the first time to distinguish benign neurofibroma from malignant peripheral nerve sheath tumor (MPNST) at our institution (n = 69) were compared to PET/CT imaging of sarcoidosis (n = 25) and early stage lung cancer (T1N0M0 tumors, n = 15) patients. RESULTS: Two NF1 patients (3%) showed a diffuse 18F-FDG uptake in the thyroid gland, 2 patients (3%) had an irregular uptake, and 7 patients (10%) had a focal uptake. Among the sarcoidosis patients, 1 showed a diffuse uptake (4%) and 1 had an irregular uptake (4%). In the early stage lung cancer group, 1 patient showed a diffuse uptake (7%) and 1 had a focal uptake (7%). NF1 patients had larger mean thyroid volume and mean SUVmax compared to sarcoidosis patients but not compared to early stage lung cancer patients. Four NF1 patients were diagnosed with multinodular goiter, 2 patients were diagnosed with benign chronic lymphocytic thyroiditis, 1 patient had metastasis to the thyroid, and 1 patient had medullary thyroid cancer. CONCLUSION: Even though NF1 patients did not show an increased risk of thyroid incidentaloma on PET/CT compared to previous studies on non-thyroid cancer patients, the incidence shows that awareness of possible thyroid disease is important.

124I PET Assessment of Response of Bone Metastases to Initial Radioiodine Treatment of Differentiated Thyroid Cancer.

Iodine-positive bone metastases (BMs) are often resistant after initial radioiodine therapy applying the standard-activity approach. A comprehensive lesion-based response study for BMs has not, to our knowledge, yet been performed. In this study, pretherapy and follow-up 124I PET/CT data on BMs from differentiated thyroid cancer patients were retrospectively analyzed to assess the relationship between absorbed dose (AD) of radiation and response after initial radioiodine treatment. METHODS: Before and after initial radioiodine therapy, patients underwent serial PET/CT scanning after administration of 20-40 MBq of 124I. The pretherapy PET data were used to segment BM volumes and to predict the average ADs after administration of dosimetry-guided 131I activity. The lower volume limit of determinability of the applied segmentation method was a sphere volume of 0.16 mL. This volume limit classified the BMs into known-volume and fixed-volume groups with their respective average and minimum ADs. Follow-up 124I and 18F-FDG PET/CT data after treatment were analyzed to assess lesion-based therapy response. Response rates at different AD thresholds were calculated and were expressed as the percentage of completely responding BMs above the respective AD threshold. BMs with a maximum extent greater than twice the PET spatial resolution were visually scored for nonuniformity. RESULTS: In total, 61 BMs in 10 patients were included, of which 46 and 15 comprised the known-volume group and the fixed-volume group, respectively. The median follow-up time was 5.6 mo (range, 3.7-23.2 mo). The median average and median minimum ADs in therapy were 183 Gy (range, 39-3,600 Gy) and 270 Gy (range, 63-1,300 Gy), respectively. A range of response rate of 70%-80% was achieved at an AD threshold range of 350-650 Gy. There were 26 BMs that were amenable to visual assessment of nonuniformity, of which two thirds (17/26) were scored as clearly nonuniform, and the majority (11/17) of these nonuniform BMs responded incompletely. CONCLUSION: Both the high AD threshold associated with high response rates and the low median AD per unit of 131I activity elucidate the difficulty in achieving therapeutic efficacy for BMs when a single standard activity is administered. The relatively high AD threshold range is possibly a result of distinct levels of spatial nonuniformity in ADs.

Imaging Intraplaque Inflammation in Carotid Atherosclerosis With 18F-Fluorocholine Positron Emission Tomography-Computed Tomography: Prospective Study on Vulnerable Atheroma With Immunohistochemical Validation.

BACKGROUND: (18)F-fluorocholine ((18)F-FCH) uptake is associated with cell proliferation and activity in tumor patients. We hypothesized that (18)F-FCH could similarly be a valuable imaging tool to identify vulnerable plaques and associated intraplaque inflammation and atheroma cell proliferation. METHODS AND RESULTS: Ten consecutive stroke patients (90% men, median age 66.5 years, range, 59.4-69.7) with ipsilateral >70% carotid artery stenosis and who underwent carotid endarterectomy were included in the study. Before carotid endarterectomy, all patients underwent positron emission tomography to assess maximum (18)F-FCH uptake in ipsilateral symptomatic carotid plaques and contralateral asymptomatic carotid arteries, which was corrected for background activity, resulting in a maximum target-to-background ratio (TBRmax). Macrophage content was assessed in all carotid endarterectomy specimens as a percentage of CD68(+)-staining per whole plaque area (plaqueCD68(+)) and as a maximum CD68(+) percentage (maxCD68(+)) in the most inflamed section/plaque. Dynamic positron emission tomography imaging demonstrated that an interval of 10 minutes between (18)F-FCH injection and positron emission tomography acquisition is appropriate for carotid plaque imaging. TBRmax in ipsilateral symptomatic carotid plaques correlated significantly with plaqueCD68(+) (Spearman's ρ=0.648, P=0.043) and maxCD68(+) (ρ=0.721, P=0.019) in the 10 corresponding carotid endarterectomy specimens. TBRmax was significantly higher (P=0.047) in ipsilateral symptomatic carotid plaques (median: 2.0; interquartile range [Q1-Q3], 1.5-2.5) compared with the contralateral asymptomatic carotid arteries (median: 1.4; Q1-Q3, 1.3-1.6). TBRmax was not significantly correlated to carotid artery stenosis (ρ=0.506, P=0.135). CONCLUSIONS: In vivo uptake of (18)F-FCH in human carotid atherosclerotic plaques correlated strongly with degree of macrophage infiltration and recent symptoms, thus (18)F-FCH positron emission tomography is a promising tool for the evaluation of vulnerable plaques. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01899014.

Dose-Response Relationship in Differentiated Thyroid Cancer Patients Undergoing Radioiodine Treatment Assessed by Means of 124I PET/CT.

UNLABELLED: The dose-response relationship in a fixed-activity approach generally applied in the treatment of differentiated thyroid cancer was assessed using (124)I PET/CT. METHODS: Pretherapeutic (124)I PET/CT images of 47 patients scheduled for radioiodine therapy were retrospectively analyzed. (124)I PET/CT images were acquired 24 and 96 h after oral administration of approximately 28 MBq of (124)I-sodium iodide. Lesions were identified as thyroid remnants or metastases (lymph node, lung, bone). After a neoteric segmentation technique allowing accurate volume estimation down to the (124)I PET spatial resolution of 0.15 mL was applied, lesions were divided into a known-volume group and a small-volume group. For the known-volume group, average lesion-absorbed dose (AD) values were calculated, whereas for the small-volume group a minimum lesion AD was estimated. Lesion response was determined on the basis of (124)I PET/CT and (131)I SPECT/CT follow-up images. A lesion not detectable on any of the follow-up images was considered a completely responding lesion. Differences in lesion AD estimations between completely and incompletely responding lesions were evaluated by Mann-Whitney U test. Moreover, receiver-operating-characteristic curves were used to test the performance of pretherapeutic (124)I PET/CT lesion AD for prediction of complete lesion response. RESULTS: In the approach of fixed radioiodine activity (3.0 ± 1.0 GBq), 89% of thyroid remnants and 69% of metastases responded completely. Except for the small-volume groups, the lesion AD of completely responding lesions was significantly higher than that of incompletely responding lesions. Using receiver-operating-characteristic curve analysis, it was shown that for the known-volume group, pretherapeutic (124)I PET/CT lesion dosimetry can be used as a prognostic tool to predict lesion-based (131)I therapy response with an area under the curve of 0.76 for remnants and 0.97 for metastases. The corresponding lesion AD threshold value maximizing correct complete response prediction was 90 Gy for remnants and 40 Gy for metastases. CONCLUSION: In a fixed-activity approach, a statistically significant dose-response relationship for both thyroid remnants and metastases using pretherapeutic (124)I PET/CT lesion dosimetry was found. The findings may be useful in patient management.

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.

Evaluation of a short dynamic 18F-fluoride PET/CT scanning method to assess bone metabolic activity in spinal orthopedics.

OBJECTIVE: A complication after spinal fusion surgery is pseudarthrosis, but its radiological diagnosis is of limited value. (18)F-fluoride PET with its ability to assess bone metabolism activity could be of value. The goal of this study was to assess the clinical feasibility of calculating the static standardized uptake value (SUV) from a short dynamic scan without the use of blood sampling, thereby obtaining all dynamic and static parameters in a scan of only 30 min. This approach was tested on a retrospective patient population with persisting pain after spinal fusion surgery. METHODS: In 16 patients, SUVs (SUV max, SUV mean) and kinetic parameters (K 1, k 2, k 3, v b, K i,NLR, K 1/k 2, k 3/(k 2 + k 3), K i,patlak) were derived from static and dynamic PET/CT scans of operated and control regions of the spine, after intravenous administration of 156-214 MBq (18)F-fluoride. Parameter differences between control and operated regions, as well as between pseudarthrosis and fused segments were evaluated. SUVmean at 30 and 60 min was calculated from kinetic parameters obtained from the dynamic data set (SUV mean,2TCM). Agreement between measured and calculated SUVs was evaluated through Bland-Altman plots. RESULTS: Overall, statistically significant differences between control and operated regions were observed for SUV max, SUV mean, K i,NLR, K i,patlak, K 1/k 2 and k 3/(k 2 + k 3). Diagnostic CT showed pseudarthrosis in 6/16 patients, while in 10/16 patients, segments were fused. Of all parameters, only those regarding the incorporation of bone [K i,NLR, K i,patlak, k 3/(k 2 + k 3)] differed statistically significant in the intervertebral disc space between the pseudarthrosis and fused patients group. The mean values of the patient-specific blood clearance rate [Formula: see text] differed statistically significant between the pseudarthrosis and the fusion group, with a p value of 0.011. This may correspond with the lack of statistical significance of the SUV values between pseudarthrosis and fused patients. Bland-Altman plots show that calculated SUV mean,2TCM values corresponded well with the measured SUV mean values. CONCLUSION: This study shows the feasibility of a 30-min dynamic (18)F-fluoride PET/CT scanning and this may provide dynamic parameters clinically relevant to the diagnosis of pseudarthrosis.

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.

Hypoxia imaging with [¹8F]HX4 PET in NSCLC patients: defining optimal imaging parameters.

BACKGROUND AND PURPOSE: [(18)F]HX4 is a promising hypoxia PET-tracer. Uptake, spatio-temporal stability and optimal acquisition parameters for [(18)F]HX4 PET imaging were evaluated in non-small cell lung cancer (NSCLC) patients. MATERIALS AND METHODS: [(18)F]HX4 PET/CT images of 15 NSCLC patients were acquired 2h and 4h after injection (p.i.). Maximum standardized-uptake-value (SUV(max)), tumor-to-blood-ratio (TBR(max)), hypoxic fraction (HF) and contrast-to-noise-ratio (CNR) were determined for all lesions. To evaluate spatio-temporal stability, DICE-similarity and Pearson correlation coefficients were calculated. Optimal acquisition-duration was assessed by comparing 30, 20, 10 and 5 min acquisitions. RESULTS: Considerable uptake (TBR >1.4) was observed in 18/25 target lesions. TBR(max) increased significantly from 2 h (1.6 ± 0.3) to 4 h p.i. (2.0 ± 0.6). Uptake patterns at 2 h and 4 h p.i. showed a strong correlation (R=0.77 ± 0.10) with a DICE similarity coefficient of 0.69 ± 0.08 for the 30% highest uptake volume. Reducing acquisition-time resulted in significant changes in SUV(max) and CNR. TBR(max) and HF were only affected for scan-times of 5 min. CONCLUSIONS: The majority of NSCLC lesions showed considerable [(18)F]HX4 uptake. The heterogeneous uptake pattern was stable between 2 h and 4 h p.i. [(18)F]HX4 PET imaging at 4 h p.i. is superior to 2 h p.i. to reach highest contrast. Acquisition time may be reduced to 10 min without significant effects on TBR(max) and HF.

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.

Characteristics of a new system for monitoring the leakage factor during regional hyperthermic isolated limb perfusion.

RATIONALE: A new system is presented and evaluated for real-time monitoring of blood leakage during hyperthermic isolated limb perfusion (HILP) surgery, the Veenstra HILP system. This system incorporates two software models to determine blood leakage: a single-nuclide algorithm and a newly developed dual-nuclide algorithm. The latter algorithm has the advantage that, in principle, it is independent of system sensitivity and thus independent of changes in geometrical efficiency. A physical description of the system is given, together with the required hardware and software specifications. METHODS: In-vitro measurements, corresponding to the intended clinical use, are presented to investigate the relevant performance characteristics of the system: count rate linearity, measurement uncertainty, response time, and accuracy. As the Veenstra HILP system provides the opportunity to use different filter settings and averaging time, the influence of these settings on the time response and measurement uncertainty is described. RESULTS: Count rate linearity was better than 1% for the count rate domain typically observed during HILP procedures. The response time of the system degrades with increasing total averaging time. In contrast, measurement uncertainty in the blood leakage factor improves with increasing radiotracer count rates and increasing total averaging time. For both blood leakage algorithms, measurement accuracy is better than 1.0 and 1.5%, respectively. CONCLUSION: Measurements have shown that the system is well suited for the real-time monitoring of blood leakage during HILP surgery. Furthermore, a good agreement was observed between the theoretical and measured response time and measurement uncertainty.