Adjunctive pascolizumab in rifampicin-susceptible pulmonary tuberculosis: proof-of-concept, partially-randomised, double-blind, placebo-controlled, dose-escalation trial.

BACKGROUND: Interleukin-4 (IL-4), increased in tuberculosis infection, may impair bacterial killing. Blocking IL-4 confers benefit in animal models. We evaluated safety and efficacy of pascolizumab (humanised anti-IL-4 monoclonal antibody) as adjunctive tuberculosis treatment. METHODS: Participants with rifampicin-susceptible pulmonary tuberculosis received a single intravenous infusion of pascolizumab or placebo; and standard 6-month tuberculosis treatment. Pascolizumab dose increased in successive cohorts: [1] non-randomised 0.05 mg/kg (n = 4); [2] non-randomised 0.5 mg/kg (n = 4); [3] randomised 2.5 mg/kg (n = 9) or placebo (n = 3); [4] randomised 10 mg/kg (n = 9) or placebo (n = 3). Co-primary safety outcome was study-drug-related grade 4 or serious adverse event (G4/SAE); in all cohorts (1-4). Co-primary efficacy outcome was week-8 sputum culture time-to-positivity (TTP); in randomised cohorts (3-4) combined. RESULTS: Pascolizumab levels exceeded IL-4 50% neutralising dose for 8 weeks in 78-100% of participants in cohorts 3-4. There were no study-drug-related G4/SAEs. Median week-8 TTP was 42 days in pascolizumab and placebo groups (p = 0.185). Rate of TTP increase was greater with pascolizumab (difference from placebo 0.011 [95% Bayesian credible interval 0.006 to 0.015] log10TTP/day. CONCLUSIONS: There was no evidence to suggest blocking IL-4 was unsafe. Preliminary efficacy findings are consistent with animal models. This supports further investigation of adjunctive anti-IL-4 interventions for tuberculosis in larger phase 2 trials.

Optimisation of the air fraction correction for lung PET/CT: addressing resolution mismatch.

BACKGROUND: Increased pulmonary [Formula: see text]F-FDG metabolism in patients with idiopathic pulmonary fibrosis, and other forms of diffuse parenchymal lung disease, can predict measurements of health and lung physiology. To improve PET quantification, voxel-wise air fractions (AF) determined from CT can be used to correct for variable air content in lung PET/CT. However, resolution mismatches between PET and CT can cause artefacts in the AF-corrected image. METHODS: Three methodologies for determining the optimal kernel to smooth the CT are compared with noiseless simulations and non-TOF MLEM reconstructions of a patient-realistic digital phantom: (i) the point source insertion-and-subtraction method, [Formula: see text]; (ii) AF-correcting with varyingly smoothed CT to achieve the lowest RMSE with respect to the ground truth (GT) AF-corrected volume of interest (VOI), [Formula: see text]; iii) smoothing the GT image to match the reconstruction within the VOI, [Formula: see text]. The methods were evaluated both using VOI-specific kernels, and a single global kernel optimised for the six VOIs combined. Furthermore, [Formula: see text] was implemented on thorax phantom data measured on two clinical PET/CT scanners with various reconstruction protocols. RESULTS: The simulations demonstrated that at [Formula: see text] iterations (200 i), the kernel width was dependent on iteration number and VOI position in the lung. The [Formula: see text] method estimated a lower, more uniform, kernel width in all parts of the lung investigated. However, all three methods resulted in approximately equivalent AF-corrected VOI RMSEs (<10%) at [Formula: see text]200i. The insensitivity of AF-corrected quantification to kernel width suggests that a single global kernel could be used. For all three methodologies, the computed global kernel resulted in an AF-corrected lung RMSE <10%  at [Formula: see text]200i, while larger lung RMSEs were observed for the VOI-specific kernels. The global kernel approach was then employed with the [Formula: see text] method on measured data. The optimally smoothed GT emission matched the reconstructed image well, both within the VOI and the lung background. VOI RMSE was <10%, pre-AFC, for all reconstructions investigated. CONCLUSIONS: Simulations for non-TOF PET indicated that around 200i were needed to approach image resolution stability in the lung. In addition, at this iteration number, a single global kernel, determined from several VOIs, for AFC, performed well over the whole lung. The [Formula: see text] method has the potential to be used to determine the kernel for AFC from scans of phantoms on clinical scanners.

Normal organ dosimetry for thyroid cancer patients treated with radioiodine as part of the multi-centre multi-national Horizon 2020 MEDIRAD project.

PURPOSE: Dosimetry is rarely performed for the treatment of differentiated thyroid cancer patients with Na[131I]I (radioiodine), and information regarding absorbed doses delivered is limited. Collection of dosimetry data in a multi-centre setting requires standardised quantitative imaging and dosimetry. A multi-national, multi-centre clinical study was performed to assess absorbed doses delivered to normal organs for differentiated thyroid cancer patients treated with Na[131I]I. METHODS: Patients were enrolled in four centres and administered fixed activities of 1.1 or 3.7 GBq of Na[131I]I using rhTSH stimulation or under thyroid hormone withdrawal according to local protocols. Patients were imaged using SPECT(/CT) at variable imaging time-points following standardised acquisition and reconstruction protocols. Whole-body retention data were collected. Dosimetry for normal organs was performed at two dosimetry centres and results collated. RESULTS: One hundred and five patients were recruited. Median absorbed doses per unit administered activity of 0.44, 0.14, 0.05 and 0.16 mGy/MBq were determined for the salivary glands of patients treated at centre 1, 2, 3 and 4, respectively. Median whole-body absorbed doses for 1.1 and 3.7 GBq were 0.05 Gy and 0.16 Gy, respectively. Median whole-body absorbed doses per unit administered activity of 0.04, 0.05, 0.04 and 0.04 mGy/MBq were calculated for centre 1, 2, 3 and 4, respectively. CONCLUSIONS: A wide range of normal organ doses were observed for differentiated thyroid cancer patients treated with Na[131I]I, highlighting the necessity for individualised dosimetry. The results show that data may be collated from multiple centres if minimum standards for the acquisition and dosimetry protocols can be achieved.

The Role of Pretherapy Quantitative Imaging and Dosimetry in Radioiodine Therapy for Advanced Thyroid Cancer.

Radioactive iodine is well established as a successful treatment for differentiated thyroid cancer (DTC), although around 15% of patients have local recurrence or develop distant metastases and may become refractory to radioactive iodine (RAI). A personalized approach to treatment, based on the absorbed radiation doses delivered and using treatments to enhance RAI uptake, has not yet been developed. Methods: We performed a multicenter clinical trial to investigate the role of selumetinib, which modulates the expression of the sodium iodide symporter, and hence iodine uptake, in the treatment of RAI-refractory DTC. The iodine uptake before and after selumetinib was quantified to assess the effect of selumetinib. The range of absorbed doses delivered to metastatic disease was calculated from pre- and posttherapy imaging, and the predictive accuracy of a theranostic approach to enable personalized treatment planning was investigated. Results: Significant inter- and intrapatient variability was observed with respect to the uptake of RAI and the effect of selumetinib. The absorbed doses delivered to metastatic lesions ranged from less than 1 Gy to 1,170 Gy. A strong positive correlation was found between the absorbed doses predicted from pretherapy imaging and those measured after therapy (r = 0.93, P < 0.001). Conclusion: The variation in outcomes from RAI therapy of DTC may be explained, among other factors, by the range of absorbed doses delivered. The ability to assess the effect of treatments that modulate RAI uptake, and to estimate the absorbed doses at therapy, introduces the potential for patient stratification using a theranostic approach. Patient-specific absorbed dose planning might be the key to more successful treatment of advanced DTC.

Iodine-131 and Iodine-131-Meta-iodobenzylguanidine Dosimetry in Cancer Therapy.

Radioactive iodine was first used for the treatment of benign thyroid disease and thyroid cancer 80 years ago. I-131 mIBG was later developed for the treatment of adult and pediatric neuroendocrine tumors. Physicists were closely involved from the outset to measure retention, to quantify uptake and to calculate radiation dosimetry. As the treatment became widespread, contrasting treatment regimes were followed, either given with empirically derived fixed levels of activity or guided according to the radiation doses delivered. As for external beam radiotherapy, individualized treatments for both thyroid cancer and neuroendocrine tumors were developed based on the aim of maximizing the radiation doses delivered to target volumes while restricting the radiation doses delivered to organs-at-risk, particularly the bone marrow. The challenge of marrow dosimetry has been met by using surrogate measures, often the blood dose for thyroid treatments and the whole-body dose in the case of treatment of neuroblastoma with I-131 mIBG. A number of studies have sought to establish threshold absorbed doses to ensure therapeutic efficacy. Although different values have been postulated, it has nevertheless been conclusively demonstrated that a fixed activity approach leads to a wide range of absorbed doses delivered to target volumes and to normal organs. Personalized treatment planning is now technically feasible with ongoing multicenter clinical trials and investigations into image quantification, biokinetic modelling and radiobiology.

A Systematic Review and Meta-Analysis of the Relationship Between the Radiation Absorbed Dose to the Thyroid and Response in Patients Treated with Radioiodine for Graves' Disease.

Background: Patients with Graves' disease are commonly treated with radioiodine. There remains controversy over whether the aim of treatment should be to achieve euthyroidism or hypothyroidism, and whether treatments should be administered with standard levels of radioactivity or personalized according to the radiation absorbed doses delivered to the thyroid. The aim of this review was to investigate whether a relationship exists between radiation absorbed dose and treatment outcome. Methods: A systematic review and meta-analysis of all reports published before February 13, 2020, were performed using PubMed, Web of Science, OVID MEDLINE, and Embase. Proportion of patients achieving nonhyperthyroid status was the primary outcome. Secondary outcomes were proportion of patients who were specifically euthyroid or hypothyroid. A random-effects meta-analysis of proportions was performed for primary and secondary outcomes, and the impact of the radiation absorbed dose on treatment outcome was assessed through meta-regression. The study is registered with PROSPERO (CRD42020175010). Results: A total of 1122 studies were identified of which 15, comprising 2303 Graves' disease patients, were eligible for the meta-analysis. A strong association was found between radiation absorbed dose and nonhyperthyroid and hypothyroid outcomes (odds ratio [OR] = 1.11 [95% confidence interval {CI} 1.08-1.14] and OR = 1.09 [CI 1.06-1.12] per 10 Gy increase). Higher rates of euthyroid outcome were found for radiation absorbed doses within the range 120-180 Gy when compared with outside this range (n = 1172, OR = 2.50 [CI 1.17-5.35], p = 0.018). A maximum euthyroid response of 38% was identified at a radiation absorbed dose of 128 Gy. Conclusions: The presented radiation absorbed dose-response relationships can facilitate personalized treatment planning for radioiodine treatment of patients with Graves' disease. Further studies are required to determine how patient-specific covariates can inform personalized treatments.

Folate and Vitamin B-12 Status Is Associated With Bone Mineral Density and Hip Strength of Postmenopausal Chinese-Singaporean Women.

The role of micronutrients such as folate and vitamin B-12 in bone quality has been widely studied with conflicting results. Ethnicity seems to play a large role on nutrient intake, as diet varies across cultures. In this study, we examined the relationships of BMD, proximal femur strength, and bone resorption with plasma folate and vitamin B-12 in a cohort of 93 healthy postmenopausal women of Chinese-Singaporean descent. The parameters examined were areal (aBMD) and volumetric BMD (vBMD) of the proximal femur and the third lumbar vertebra (L3), total body aBMD, proximal femur bending, compressive and impact strength indices (composite strength indices) and circulating levels of C-telopeptide of type I collagen. Eighteen participants (19.4%) had aBMD in the osteoporotic range (osteoporosis group), 59 (63.4%) in the osteopenic range (osteopenia group), and the remaining 16 (17.2%) in the normal range (normal BMD group). Circulating folate levels were significantly higher in the normal BMD group compared with the osteoporosis group. Using linear regression analysis, we found that overall, aBMD and vBMD are positively associated with folate concentrations, whereas composite strength indices were positively associated with vitamin B-12 concentrations. These findings support the existing literature and suggest a link between levels of circulating folate/vitamin B-12 and BMD/bone strength in the cohort examined. Further investigation is needed to examine if individuals with inadequate circulating levels of these nutrients could decrease their risk for fragility fractures through better nutrition or vitamin supplementation. © 2020 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research © 2020 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Setting up a quantitative SPECT imaging network for a European multi-centre dosimetry study of radioiodine treatment for thyroid cancer as part of the MEDIRAD project.

BACKGROUND: Differentiated thyroid cancer has been treated with radioiodine for almost 80 years, although controversial questions regarding radiation-related risks and the optimisation of treatment regimens remain unresolved. Multi-centre clinical studies are required to ensure recruitment of sufficient patients to achieve the statistical significance required to address these issues. Optimisation and standardisation of data acquisition and processing are necessary to ensure quantitative imaging and patient-specific dosimetry. MATERIAL AND METHODS: A European network of centres able to perform standardised quantitative imaging of radioiodine therapy of thyroid cancer patients was set-up within the EU consortium MEDIRAD. This network will support a concurrent series of clinical studies to determine accurately absorbed doses for thyroid cancer patients treated with radioiodine. Five SPECT(/CT) systems at four European centres were characterised with respect to their system volume sensitivity, recovery coefficients and dead time. RESULTS: System volume sensitivities of the Siemens Intevo systems (crystal thickness 3/8″) ranged from 62.1 to 73.5 cps/MBq. For a GE Discovery 670 (crystal thickness 5/8″) a system volume sensitivity of 92.2 cps/MBq was measured. Recovery coefficients measured on three Siemens Intevo systems show good agreement. For volumes larger than 10 ml, the maximum observed difference between recovery coefficients was found to be ± 0.02. Furthermore, dead-time coefficients measured on two Siemens Intevo systems agreed well with previously published dead-time values. CONCLUSIONS: Results presented here provide additional support for the proposal to use global calibration parameters for cameras of the same make and model. This could potentially facilitate the extension of the imaging network for further dosimetry-based studies.

Tissue mimicking materials for imaging and therapy phantoms: a review.

Tissue mimicking materials (TMMs), typically contained within phantoms, have been used for many decades in both imaging and therapeutic applications. This review investigates the specifications that are typically being used in development of the latest TMMs. The imaging modalities that have been investigated focus around CT, mammography, SPECT, PET, MRI and ultrasound. Therapeutic applications discussed within the review include radiotherapy, thermal therapy and surgical applications. A number of modalities were not reviewed including optical spectroscopy, optical imaging and planar x-rays. The emergence of image guided interventions and multimodality imaging have placed an increasing demand on the number of specifications on the latest TMMs. Material specification standards are available in some imaging areas such as ultrasound. It is recommended that this should be replicated for other imaging and therapeutic modalities. Materials used within phantoms have been reviewed for a series of imaging and therapeutic applications with the potential to become a testbed for cross-fertilization of materials across modalities. Deformation, texture, multimodality imaging and perfusion are common themes that are currently under development.

Comparison of 68Ga-DOTANOC with 18F-FDG using PET/MRI imaging in patients with pulmonary tuberculosis.

We compared the somatostatin analog radioligand, DOTANOC, with FDG, to determine whether there was increased detection of active or sub-clinical lesions in pulmonary tuberculosis (TB) with DOTANOC. Three groups were recruited: (1) active pulmonary TB; (2) IGRA-positive household TB contacts; (3) pneumonia (non-TB). DOTANOC PET/MRI followed by FDG PET/MRI was performed in active TB and pneumonia groups. TB contacts underwent FDG PET/MRI, then DOTANOC PET/MRI if abnormalities were detected. Quantitative and qualitative analyses were performed for total lung and individual lesions. Eight active TB participants, three TB contacts and three pneumonia patients had paired PET/MRI scans. In the active TB group, median SUVmax[FDG] for parenchymal lesions was 7.69 (range 3.00-15.88); median SUVmax[DOTANOC] was 2.59 (1.48-6.40). Regions of tracer uptake were fairly similar for both radioligands, albeit more diffusely distributed in the FDG scans. In TB contacts, two PET/MRIs had parenchymal lesions detected with FDG (SUVmax 5.50 and 1.82), with corresponding DOTANOC uptake < 1. FDG and DOTANOC uptake was similar in pneumonia patients (SUVmax[FDG] 4.17-6.18; SUVmax[DOTANOC] 2.92-4.78). DOTANOC can detect pulmonary TB lesions, but FDG is more sensitive for both active and sub-clinical lesions. FDG remains the preferred ligand for clinical studies, although DOTANOC may provide additional value for pathogenesis studies.

Standardised quantitative radioiodine SPECT/CT Imaging for multicentre dosimetry trials in molecular radiotherapy.

The SEL-I-METRY trial (EudraCT No 2015-002269-47) is the first multicentre trial to investigate the role of 123I and 131I SPECT/CT-based tumour dosimetry to predict response to radioiodine therapy. Standardised dosimetry methodology is essential to provide a robust evidence-base for absorbed dose-response thresholds for molecular radiotherapy (MRT). In this paper a practical standardised protocol is used to establish the first network of centres with consistent methods of radioiodine activity quantification. Nine SPECT/CT systems at eight centres were set-up for quantitative radioiodine imaging. The dead-time of the systems was characterised for up to 2.8 GBq 131I. Volume dependent calibration factors were measured on centrally reconstructed images of 123I and 131I in six (0.8-196 ml) cylinders. Validation of image quantification using these calibration factors was performed on three systems, by imaging a 3D-printed phantom mimicking a patient's activity distribution. The percentage differences between the activities measured in the SPECT/CT image and those measured by the radionuclide calibrator were calculated. Additionally uncertainties on the SPECT/CT-based activities were calculated to indicate the limit on the quantitative accuracy of this method. For systems set-up to image high 131I count rates, the count rate versus activity did not peak below 2.8 GBq and fit a non-paralysable model. The dead-times and volume-dependent calibration factors were comparable between systems of the same model and crystal thickness. Therefore a global calibration curve could be fitted to each. The errors on the validation phantom activities' were comparable to the measurement uncertainties derived from uncertainty analysis, at 10% and 16% on average for 123I and 131I respectively in a 5 cm sphere. In conclusion, the dead-time and calibration factors varied between centres, with different models of system. However, global calibration factors may be applied to the same system model with the same crystal thickness, to simplify set-up of future multi-centre MRT studies.

Physics aspects of setting up a multicenter clinical trial involving internal dosimetry of radioiodine treatment of differentiated thyroid cancer.

The field of molecular radiotherapy is expanding rapidly, with the advent of many new radiotherapeutics for the treatment of common as well as for rare cancers. Treatment outcome is dependent on the absorbed doses delivered to target volumes and to healthy organs-at-risk, which are shown to vary widely from fixed administrations of activity. There have been significant developments in quantitative imaging and internal dosimetry in recent years, although clinical implementation of these methods has been slow in comparison with external beam radiotherapy, partly due to there being relatively few patients treated at single centers. Multicenter clinical trials are therefore essential to acquire the data required to ensure best practice and to develop the personalized treatment planning that this area is well suited to, due to the unrivalled opportunity to image the therapeutic drug in vivo. Initial preparation for such trials requires a significant effort in terms of resources and trial design. Imaging systems in participating centers must be characterized and set up for quantitative imaging to allow for collation of data. Data transfer for centralized processing is usually necessary but is hindered in some cases by data protection regulations and local logistics. Recent multicenter clinical trials involving radioiodine therapy have begun to establish the procedures necessary for quantitative SPECT imaging in a multicenter setting using standard and anthropomorphic phantoms. The establishment of national and international multicenter imaging and dosimetry networks will provide frameworks to develop and harmonize best practice with existing therapeutic procedures and to ensure rapid and optimized clinical implementation of new radiotherapeutics across all centers of excellence that offer molecular radiotherapy. This will promote networks and collaborations that can provide a sound basis for further developments and will ensure that nuclear medicine maintains a key role in future developments.

Cardiac motion and spillover correction for quantitative PET imaging using dynamic MRI.

PURPOSE: Cardiac positron emission tomography/magnetic resonance imaging (PET/MRI) acquisition presents novel clinical applications thanks to the combination of viability and metabolic imaging (PET) and functional and structural imaging (MRI). However, the resolution of PET, as well as cardiac and respiratory motion in nongated cardiac imaging acquisition protocols, leads to a reduction in image quality and severe quantitative bias. Respiratory or cardiac motion is customarily addressed with gated reconstruction which results in higher noise. METHODS: Inspired by a method that has been used in brain PET, a practical correction approach, designed to overcome these existing limitations for quantitative PET imaging, was developed and applied in the context of cardiac PET/MRI. The correction approach for PET data consists of computing the mean density map of each underlying moving region, as obtained with MRI, and translating them to the PET space taking into account the PET spatial and temporal resolution. Using these tissue density maps, the method then constructs a system of linear equations that models the activity recovery and cross-contamination coefficients, which can be solved for the true activity values. Physical and numerical cardiac phantoms were employed in order to quantify the proposed correction. The full correction pipeline was then used to assess differences in metabolic function between scar and healthy myocardium in eight patients with recent acute myocardial infarction using [11 C]-acetate. Data from ten additional patients, injected with [18 F]-FDG, were used to compare the method to the standard electrocardiography (ECG)-gated approach. RESULTS: The proposed method resulted in better recovery (from 32% to 95% on the simulated phantom model) and less residual activity than the standard approach. Higher signal-to-noise and contrast-to-noise ratios than ECG-gating were also witnessed (Signal-to-noise ratio (SNR) increased from 2.92 to 5.24, contrast-to-noise ratio (CNR) increased from 62.9 to 145.9 when compared to a four-gate reconstruction). Finally, the relevance of this correction using [11 C]-acetate PET patient data, for which erroneous physiological conclusions could have been made based on the uncorrected data, was established as the correction led to the expected clinical results. CONCLUSIONS: An efficient and simple method to correct for the quantitative biases in PET measurements caused by cardiac motion has been developed. Validation experiments using phantom and patient data showed improved accuracy and reliability with this approach when compared to simpler strategies such as gated acquisition or optimal regions of interest (ROI).

Association of Insulin Resistance with Bone Strength and Bone Turnover in Menopausal Chinese-Singaporean Women without Diabetes.

Insulin resistance (IR) is accompanied by increased areal or volumetric bone mineral density (aBMD or vBMD), but also higher fracture risk. Meanwhile, imbalances in bone health biomarkers affect insulin production. This study investigates the effect of IR on proximal femur and lumbar spine BMD, femoral neck bending, compressive and impact strength indices (Composite Strength Indices) and circulating levels of parathyroid hormone (PTH), C-telopeptide of Type I collagen (CTx-1) and 25(OH) Vitamin D3, in a cohort of 97 healthy, non-obese, menopausal Chinese-Singaporean women. Lumbar spine aBMD was inversely associated with IR and dependent on lean body mass (LBM) and age. No such associations were found for vBMD of the third lumbar vertebra, aBMD and vBMD of the proximal femur, or circulating levels of PTH, CTx-1 and 25(OH) Vitamin D3. Composite Strength Indices were inversely associated with IR and independent of LBM, but after adjusting for fat mass and age, this association remained valid only for the impact strength index. Composite Strength Indices were significantly lower in participants with a high degree of IR. Our findings on IR and Composite Strength Indices relationships were in agreement with previous studies on different cohorts, but those on IR and BMD associations were not.

Multi institutional quantitative phantom study of yttrium-90 PET in PET/MRI: the MR-QUEST study.

BACKGROUND: Yttrium-90 (90Y) radioembolization involves the intra-arterial delivery of radioactive microspheres to treat hepatic malignancies. Though this therapy involves careful pre-treatment planning and imaging, little is known about the precise location of the microspheres once they are administered. Recently, there has been growing interest post-radioembolization imaging using positron-emission tomography (PET) for quantitative dosimetry and identifying lesions that may benefit from additional salvage therapy. In this study, we aim to measure the inter-center variability of 90Y PET measurements as measured on PET/MRI in preparation for a multi-institutional prospective phase I/II clinical trial. Eight institutions participated in this study and followed a standardized phantom filling and imaging protocol. The NEMA NU2-2012 body phantom was filled with 3 GBq of 90Y chloride solution. The phantom was imaged for 30 min in listmode on a Siemens Biograph mMR non-TOF PET/MRI scanner at five time points across 10 days (0.3-3.0 GBq). Raw PET data were sent to a central site for image reconstruction and data analysis. Images were reconstructed with optimal parameters determined from a previous study. Volumes of interest (VOIs) matching the known sphere diameters were drawn on the vendor-provided attenuation map and propagated to the PET images. Recovery coefficients (RCs) and coefficient of variation of the RCs (COV) were calculated from these VOIs for each sphere size and activity level. RESULTS: Mean RCs ranged from 14.5 to 75.4%, with the lowest mean RC coming from the smallest sphere (10 mm) on the last day of imaging (0.16 MBq/ml) and the highest mean RC coming from the largest sphere (37 mm) on the first day of imaging (2.16 MBq/ml). The smaller spheres tended to exhibit higher COVs. In contrast, the larger spheres tended to exhibit lower COVs. COVs from the 37 mm sphere were < 25.3% in all scans. For scans with ≥ 0.60 MBq/ml, COVs were ≤ 25% in spheres ≥ 22 mm. However, for all other spheres sizes and activity levels, COVs were usually > 25%. CONCLUSIONS: Post-radioembolization dosimetry of lesions or other VOIs ≥ 22 mm in diameter can be consistently obtained (< 25% variability) at a multi-institutional level using PET/MRI for any clinically significant activity for 90Y radioembolization.

A comparison of 18F-FDG PET/MR with PET/CT in pulmonary tuberculosis.

PURPOSE: PET/computed tomography (CT) has been shown to detect lesions in patients with pulmonary tuberculosis (PTB) and may be useful for assessing PTB disease in clinical research studies. However, radiation dose is of concern for clinical research in individuals with an underlying curable disease. This study aimed to determine whether PET/MR is equivalent to PET/CT in PTB. MATERIALS AND METHODS: Ten patients with microbiologically confirmed PTB were recruited. Patients received 129.0±4.1 MBq of fluorine-18-fluorodeoxyglucose. Five of the 10 patients underwent a PET/MR scan, followed by PET/CT. The remaining five were first imaged on the PET/CT, followed by the PET/MRI. PET acquisition began at 66.7±14.4 min (mean±SD) after injection when performing PET/MR first (PET/CT: 117.2±5.6 min) and 92.4±7.6 min when patients were imaged on PET/MR second (PET/CT: 61.1±3.9 min). PET data were reconstructed iteratively with Ordinary-Poisson Ordered-Subset Expectation-Maximization and reconstruction parameters were matched across the two scanners. A visual lesion detection task and a standardized uptake value (SUV) analysis were carried out. The CT Hounsfield unit values of PTB lesions were also compared with MR-based attenuation correction mu-map tissue classes. RESULTS: A total of 108 PTB lesions were detected on PET/MR and 112 on PET/CT. SUV analysis was carried out on 50 of these lesions that were observed with both modalities. Mean standardized uptake value (SUVmean) and maximum standardized uptake value (SUVmax) were significantly lower on PET/MR (SUVmean: 2.6±1.4; SUVmax: 4.3±2.5) than PET/CT (SUVmean: 3.5±1.5; SUVmax: 5.3±2.4). CONCLUSION: PET/MR visual performance was shown to be comparable to PET/CT in terms of the number of PTB lesions detected. SUVs were significantly lower on PET/MR. Dixon-based attenuation correction underestimates the linear attenuation coefficient of PTB lesions, resulting in lower SUVs compared with PET/CT. However, the use of PET/MR to measure the response of lung lesions to assess response to treatment in research studies is unlikely to be affected by these differences in quantification.

A Novel Approach to CT, MR, and PET Examination of Patients with Infections Requiring Stringent Airborne Precautions.

PURPOSE: To investigate the feasibility of using a modified portable isolation chamber, which conforms to Centers for Disease Control and Prevention (CDC) isolation requirements, in the imaging of infectious patients. MATERIALS AND METHODS: This study was approved by the ethics committee, and all participants gave written informed consent. In this prospective study, the isolation chamber was assessed for computed tomographic (CT), magnetic resonance (MR), and positron emission tomographic (PET) image uniformity and noise by using uniform phantoms. For each modality, equivalent phantom examinations were performed without the isolation chamber. Paired analyses of the differences from these baseline values were conducted by finding the mean difference in the matched sections for each image quality parameter. A potential increase in CT patient dose was assessed, and MR radiofrequency (RF) interference was monitored. Eight participants with active pulmonary tuberculosis (mean age, 48.1 years; age range, 26-88 years; five men, three women) were then examined within a hybrid PET/MR imager. The 95% confidence intervals for the difference in the two matched population means were determined by using the two-sided t distribution for each of the phantom study imaging modalities. RESULTS: Phantom images were evaluated for image uniformity and noise. Increased image noise can affect low contrast resolution, which has the potential to mimic or mask abnormalities when the differences between healthy and diseased tissues are small; clinically, CT image noise is maintained at a constant level with dose modulation. Increased attenuation of annihilation photons, when not corrected for, could lead to photopenic areas on the PET image; PET image nonuniformity complied with guidelines. Artifacts on the MR image due to RF noise spikes could mask abnormalities; paired analysis of variations in MR imaging mean signal-to-noise ratio and uniformity from baseline were within 5% for both gradient-echo and spin-echo sequences. In the eight participants who underwent imaging, the increased radiation dose for the attenuation of the isolation chamber would have resulted in a mean increase in patient size-specific dose estimate of 0.32 mGy ± 0.04 (standard deviation). The RF noise assessment revealed no prominent increase at any frequency band. The eight participants were examined within the isolation chamber without incident. CONCLUSION A modified portable isolation chamber, which conforms to CDC infection control guidelines, was found to be feasible within the confines of CT, MR imaging, and PET environments.