Whole Body Research Articles

Bone Scintigraphy in Cardiac Transthyretin-Related Amyloidosis: A Novel Time-Saving Tool for Semiquantitative Analysis, with Good Potential for Predicting Different Etiologies

(1) Background: The visual and semiquantitative analysis of Technetium-99metastable-3,3-diphospono-1,2-propanodicarboxylic acid (99mTc-DPD) bone scintigraphy is promising for diagnosing cardiac amyloidosis but time-consuming. We validated a faster method, the geometric mean (GM) method with a semi-automated workflow, for heart–whole body (WB) ratio (H/WBr), heart retention (Hr), and WB retention (WBr) calculations compared to the classic method (CM) established in the literature. The capability of semiquantitative scintigraphy indexes to differentiate the etiology in transthyretin-related cardiac amyloidosis (cATTR) patients was investigated. (2) Methods: H/WBr, Hr, and WBr were calculated by extracting counts for WB, kidneys, bladder, and heart on early and late planar image scans and applying background, scan-time, and decay corrections, using CM and GM both on a referring workstation and on a semi-automated workflow in external software. The comparison between CM and GM was assessed with Pearson’s correlation, Lin’s Concordance Correlation Coefficient (CCC), and Bland–Altman analysis. H/WBr, Hr, and WBr and several clinical variables were used to implement LASSO, Random Forest (RF), and Neural Network (NN) models to predict mutated and wild-type ATTR etiologies. ROC curves and AUC were calculated. (3) Results: Hr, WBr, and H/WBr using CM and GM were highly correlated. Bland–Altman analysis between CM and GM showed biases of 0.12% [CI:0.04%;0.19%] for H/WBr, 0.07% [CI: 0.01%; 0.13%] for Hr, and -0.50% [CI: −1.22%; 0.22%] for WBr. LASSO and NN models had good performance in predicting etiologies with AUC values of 87.3% and 73.6%, respectively. The RF model showed a poorer AUC of 55.8%. (4) Conclusions: The GM in the assisted workflow was validated against the CM. LASSO and NN approaches allowed a good prediction performance to be obtained for patient etiology.

PET/CT imaging of differentiated and medullary thyroid carcinoma using the novel SSTR-targeting peptide [18F]SiTATE - first clinical experiences.

The novel 18F-labeled somatostatin receptor (SSTR)-directed radiotracer [18F]SiTATE demonstrated promising results for the imaging of various SSTR-expressing tumor types. Although thyroid carcinomas (TC) express SSTR, data on [18F]SiTATE PET/CT imaging in TC are lacking. This study explores the use of [18F]SiTATE PET/CT in a patient cohort with histologically proven TC. As part of a prospective observational study at a single tertiary cancer center, 21 patients with TC (10 medullary (MTC) and 11 differentiated (DTC)) who underwent at least one [18F]SiTATE PET/CT were included (37 scans in total). Mean SUVmax and SUVmean of tumoral lesions, mean total-tumor-volume (TTV), and whole-body (WB)-SUVmax and WB-SUVmean on PET with their standard deviations (SDs) were determined. PET parameters were correlated to clinical parameters including tumor marker levels (thyroglobulin for DTC, calcitonin for MTC). 89 lesions were included in the analysis. Metastases were localized in the bone, lymph nodes, lung, soft tissue, and thyroid bed. Osseous (31 lesions; SUVmax 8.6 ± 8.0; SUVmean 5.8 ± 5.4) and nodal (37 lesions; SUVmax 8.7 ± 7.8; SUVmean 5.7 ± 5.4) metastases showed the highest uptake. The MTC disease burden on PET significantly correlated with the calcitonin tumor marker level (e.g., TTV: r = 0.771, r2 = 0.594, p = 0.002). For DTC, no such correlation was present. Our data demonstrate high feasibility of [18F]SiTATE PET/CT in a small cohort of patients with MTC and DTC. The use of [18F]SiTATE may overcome logistical disadvantages of 68Ga-based tracers and facilitate SSTR-targeted PET/CT imaging of thyroid carcinoma.

[18F]FDG whole-body PET-MR including an integrated breast MR protocol for locoregional and distant staging in breast cancer patients—a feasibility study

PurposeTo investigate in a feasibility study the combination of [18F]FDG whole-body (WB) positron emission tomography-magnetic resonance (PET-MR), including an integrated breast MR within a single protocol for locoregional and distant staging in breast cancer patients.MethodsConsecutive patients with breast cancer diagnoses according to conventional imaging modalities (full-field digital mammography (FFDM) and ultrasound (US)) were prospectively included. All patients underwent [18F]FDG WB PET-MR, including an integrated dedicated breast MR (prone position) and WB PET-MR (supine position) protocol. Results of [18F]FDG WB PET-MR, including integrated breast MR, versus conventional imaging modalities were compared.ResultsFrom April 2021–April 2022, 28 patients were included. On conventional imaging, cT1-2 breast cancer was present in 22 (FFDM) and 23 (US) out of 28 patients. With regard to clinical nodal status, eight patients were considered cN0, eighteen cN1 (1-3 suspicious lymph nodes), and two patients were cN2 (four suspicious axillary lymph nodes/internal mammary lymph node metastasis). [18F]FDG WB PET-MR, including an integrated breast MR protocol, upstaged clinical tumor status in two patients and clinical nodal status in nine patients according to both [18F]FDG WB PET-MR and breast MR findings. In addition, distant metastases were detected in three patients (liver/bone), and another patient was diagnosed with a synchronous primary tumor (lung cancer).Conclusion[18F]FDG WB PET-MR, including an integrated breast MR within a single protocol in breast cancer patients, is feasible and provides a promising new approach in breast cancer patients with regard to locoregional and distant staging.Critical relevance statement[18F]FDG whole-body PET-MR, including an integrated breast MR protocol, is feasible and allows locoregional and distant staging within a single imaging exam in breast cancer patients.Key Points[18F]FDG PET-MR allows the combination of breast MR and whole-body staging.Therefore, a single protocol of whole-body [18F]FDG PET-MR, including an integrated breast MRI, is investigated.[18F]FDG PET-MR, including an integrated breast MR is feasible and can be considered in daily clinical practice.Graphical

The prenatal assimilation of minerals and metals in nestlings of a small passerine bird

Although certain metals can reach their highest concentrations in tissues of newly hatched nestlings, their sources have yet to be fully elucidated. Evidence for the differentiation of body reserves, including some chemical elements, during avian embryonic life and early post-hatching period is limited mostly to studies on poultry. Here, we present novel findings on the bioaccumulation and egg-to-nestling transfer of 10 minerals and metals, including non-essential potentially toxic chemical elements (Cu, Ni Cd, Pb, Zn, Ag, Mg, Fe, Co and Ca) in the tissues of the gastrointestinal tract (GT), whole body (WB) and carcass (CA) of nestlings of a small passerine bird, the Eurasian Reed Warbler Acrocephalus scirpaceus, breeding in an intensively fertilized fishpond habitat. Our findings show that concentrations of metals that are relevant to contaminated systems (Cu, Ni, Cd, Pb, Zn, Fe and Co) are the highest in GT tissues across all the nestling age classes examined (from hatching to day 9 of life). The important question emerged from our findings: why the hatchlings were characterized by higher metal concentrations in GT, WB and CA compared to older nestlings. We suggest that the prenatal accumulation of chemical elements assimilated from egg contents, and their subsequent utilization for building various tissues/internal organs by the growing embryo, is a reasonable explanation for this finding. More specifically, the potential functional mechanism explaining the highest concentrations of some trace metals in hatchlings seems to be associated with an extremely high rate of utilization of residual yolk metal resources that survived from the embryonic until the post-natal period. On the basis of our own work and literature data, we identified a presumable significant discrepancy in the actual rate of egg-to-nestling and egg-to-embryo metal transfer due to the eggshell being ignored (a commonly occurrence), and only the egg contents being treated as the basic repository of chemical elements for developing embryos. Much more research is needed on the prenatal assimilation and subsequent accumulation of chemical elements in a developing avian embryo, representing both the transition from near-to-hatching embryos to hatchlings, and then to older nestlings.

Upper- vs. Whole-Body Cooling During Exercise with Thermal Protective Clothing in the Heat.

INTRODUCTION: Firefighters operating in hot environments face challenges from protective garments that restrict heat dissipation, resulting in increased core temperature, thermal discomfort, and performance decline. Cooling vests represent a viable solution. The study aim was to compare effectiveness of the same amount of cooling power to the upper body (UB) or whole body (WB) in alleviating thermoregulatory and physiological stress, enhancing cognitive function, and reducing ratings of thermal discomfort and exertion, during 60 min of exercise in a hot environment (40°C, 40% relative humidity) while wearing firefighter turnout gear.METHODS: Eight healthy individuals (27.5 ± 3 y) participated in three conditions with either no cooling (Control) or active cooling with a liquid perfused shirt (UB cooling), or with a liquid perfused shirt and pants (WB cooling). In each trial, subjects performed three sets of 15 min of stepping (20 steps ⋅ min-1) and 5 min of rest.RESULTS: Both cooling strategies were beneficial compared to having no cooling at all. Subjects could only complete two exercise bouts during Control, but they completed all three bouts with active cooling. WB cooling provided an advantage over UB cooling for core and skin temperature, and thermal comfort and sensation. The advantage in minimizing the increase in core temperature was only evident during the third exercise bout.DISCUSSION: Active cooling is advantageous under these conditions. WB cooling provided some benefits vs UB cooling during heavy intensity exercise; however, it is uncertain whether these benefits would be observed during light-to-moderate exercise, which more likely reflects an actual firefighting scenario.Mansouri F, Talebian Nia M, Villar R, Cornish SM, Giesbrecht GG. Upper- vs. whole-body cooling during exercise with thermal protective clothing in the heat. Aerosp Med Hum Perform. 2024; 95(9):659-666.

Dose estimation in patients from different protocols of 18F-FDG PET/CT studies and analysis of optimization strategies.

This study aimed to evaluate the dose in different protocols of 18F-2-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (PET/CT) procedure. The retrospective study involves 207 patients with confirmed malignancies who underwent PET/CT. Effective dose (E) from PET was estimated based on injected activity and dose coefficient as per International Commission on Radiation Protection (ICRP) 128. Estimation of E from CT was done utilizing the dose length product (DLP) method and conversion factors as per ICRP 102. There was a significant statistical difference observed in E between different PET/CT protocols (P < .001). E of PET in the whole body (WB) was found to be 4.9±0.9mSv, whereas mean volume computed tomography dose indexvol, DLP, and E of CT in WB were 7.0±0.2mGy, 674.3±80.7mGy.cm, and 10.1±1.2mSv, respectively. No linear correlation was seen between the size-specific dose estimate and E of CT (r=-0.003; P = .978). The total mean E in WB PET/CT was 17.0±1.7mSv. CT dose was contributing more than PET dose in all protocols except brain PET/CT. Optimization strategies can be evaluated only if monitored periodically.

Detection of cancer-associated cachexia in lung cancer patients using whole-body [18F]FDG-PET/CT imaging: A multi-centre study.

Cancer-associated cachexia (CAC) is a metabolic syndrome contributing to therapy resistance and mortality in lung cancer patients (LCP). CAC is typically defined using clinical non-imaging criteria. Given the metabolic underpinnings of CAC and the ability of [18F]fluoro-2-deoxy-D-glucose (FDG)-positron emission tomography (PET)/computer tomography (CT) to provide quantitative information on glucose turnover, we evaluate the usefulness of whole-body (WB) PET/CT imaging, as part of the standard diagnostic workup of LCP, to provide additional information on the onset or presence of CAC. This multi-centre study included 345 LCP who underwent WB [18F]FDG-PET/CT imaging for initial clinical staging. A weight loss grading system (WLGS) adjusted to body mass index was used to classify LCP into 'No CAC' (WLGS-0/1 at baseline prior treatment and at first follow-up: N=158, 51F/107M), 'Dev CAC' (WLGS-0/1 at baseline and WLGS-3/4 at follow-up: N=90, 34F/56M), and 'CAC' (WLGS-3/4 at baseline: N=97, 31F/66M). For each CAC category, mean standardized uptake values (SUV) normalized to aorta uptake (<SUVaorta>) and CT-defined volumes were extracted for abdominal and visceral organs, muscles, and adipose-tissue using automated image segmentation of baseline [18F]FDG-PET/CT images. Imaging and non-imaging parameters from laboratory tests were compared statistically. A machine-learning (ML) model was then trained to classify LCP as 'No CAC', 'Dev CAC', and 'CAC' based on their imaging parameters. SHapley Additive exPlanations (SHAP) analysis was employed to identify the key factors contributing to CAC development for each patient. The three CAC categories displayed multi-organ differences in <SUVaorta>. In all target organs, <SUVaorta> was higher in the 'CAC' cohort compared with 'No CAC' (P<0.01), except for liver and kidneys, where <SUVaorta> in 'CAC' was reduced by 5%. The 'Dev CAC' cohort displayed a small but significant increase in <SUVaorta> of pancreas (+4%), skeletal-muscle (+7%), subcutaneous adipose-tissue (+11%), and visceral adipose-tissue (+15%). In 'CAC' patients, a strong negative Spearman correlation (ρ=-0.8) was identified between <SUVaorta> and volumes of adipose-tissue. The machine-learning model identified 'CAC' at baseline with 81% of accuracy, highlighting <SUVaorta> of spleen, pancreas, liver, and adipose-tissue as most relevant features. The model performance was suboptimal (54%) when classifying 'Dev CAC' versus 'No CAC'. WB [18F]FDG-PET/CT imaging reveals groupwise differences in the multi-organ metabolism of LCP with and without CAC, thus highlighting systemic metabolic aberrations symptomatic of cachectic patients. Based on a retrospective cohort, our ML model identified patients with CAC with good accuracy. However, its performance in patients developing CAC was suboptimal. A prospective, multi-centre study has been initiated to address the limitations of the present retrospective analysis.

Effects of Two Types of Resistance Training Modalities (Hypertrophy vs. Contrast Training) on Bone Parameters in a Group of Healthy Elderly Women

The aim of the present study was to explore the effects of two types of resistance training modalities (hypertrophy training vs. contrast training) on bone health parameters in a group of healthy elderly women. Forty-nine healthy elderly women whose ages range between 60 and 70 years were included in this study. The study population was randomly divided into three groups: hypertrophy training group (HTG; n=16), contrast training group (CTG; n=16) and control group (CG; n=17). Bone mineral density (BMD) values at the whole body (WB), lumbar spine (L1-L4), total hip (TH) and femoral neck (FN) were measured by DXA before and after 12 months of resistance training. Composite indices of femoral neck strength were calculated. WB BMD, L1-L4 BMD, TH BMD and FN BMD increased in the contrast training group. WB BMD and L1-L4 BMD increased in the hypertrophy training group, while TH BMD and FN BMD remained unchanged. Significant decreases in WB BMD, L1-L4 BMD, TH BMD and FN BMD were observed in the control group. The contrast training group showed the highest improvements in BMD values compared to the two other groups. Both experimental groups (HTG and CTG) showed similar significant improvements in composite indices of femoral neck strength and muscular strength. In conclusion, contrast training and hypertrophy training can stimulate bone gain at clinically important sites of osteoporotic fractures in elderly women.

Image quality of whole-body diffusion MR images comparing deep-learning accelerated and conventional sequences.

To compare the image quality of deep learning accelerated whole-body (WB) with conventional diffusion sequences. Fifty consecutive patients with bone marrow cancer underwent WB-MRI. Two experts compared axial b900 s/mm2 and the corresponding maximum intensity projections (MIP) of deep resolve boost (DRB) accelerated diffusion-weighted imaging (DWI) sequences (time of acquisition: 6:42 min) against conventional sequences (time of acquisition: 14 min). Readers assessed paired images for noise, artefacts, signal fat suppression, and lesion conspicuity using Likert scales, also expressing their overall subjective preference. Signal-to-noise and contrast-to-noise ratios (SNR and CNR) and the apparent diffusion coefficient (ADC) values of normal tissues and cancer lesions were statistically compared. Overall, radiologists preferred either axial DRB b900 and/or corresponding MIP images in almost 80% of the patients, particularly in patients with a high body-mass index (BMI > 25 kg/m2). In qualitative assessments, axial DRB images were preferred (preferred/strongly preferred) in 56-100% of cases, whereas DRB MIP images were favoured in 52-96% of cases. DRB-SNR/CNR was higher in all normal tissues (p < 0.05). For cancer lesions, the DRB-SNR was higher (p < 0.001), but the CNR was not different. DRB-ADC values were significantly higher for the brain and psoas muscles, but not for cancer lesions (mean difference: + 53 µm2/s). Inter-class correlation coefficient analysis showed good to excellent agreement (95% CI 0.75-0.93). DRB sequences produce higher-quality axial DWI, resulting in improved MIPs and significantly reduced acquisition times. However, differences in the ADC values of normal tissues need to be considered. Deep learning accelerated diffusion sequences produce high-quality axial images and MIP at reduced acquisition times. This advancement could enable the increased adoption of Whole Body-MRI for the evaluation of patients with bone marrow cancer. Deep learning reconstruction enables a more than 50% reduction in acquisition time for WB diffusion sequences. DRB images were preferred by radiologistsin almost 80% of cases due to fewer artefacts, improved background signal suppression, higher signal-to-noise ratio, and increased lesion conspicuity in patients with higher body mass index. Cancer lesion diffusivity from DRB images was not different from conventional sequences.

Accuracy of patient-specific I-131 dosimetry using hybrid whole-body planar-SPECT/CT I-123 and I-131 imaging

PurposeThis study aimed to assess the accuracy of patient-specific absorbed dose calculations for tumours and organs at risk in radiopharmaceutical therapy planning, utilizing hybrid planar-SPECT/CT imaging.MethodsThree Monte Carlo (MC) simulated digital patient phantoms were created, with time-activity data for mIBG labelled to I-123 (LEHR and ME collimators) and I-131 (HE collimator). The study assessed the accuracy of the mean absorbed doses for I-131-mIBG therapy treatment planning. Multiple planar whole-body (WB) images were simulated (between 1 to 72 h post-injection (p.i)). The geometric-mean image of the anterior and posterior WB images was calculated, with scatter and attenuation corrections applied. Time-activity curves were created for regions of interest over the liver and two tumours (diameters: 3.0 cm and 5.0 cm) in the WB images. A corresponding SPECT study was simulated at 24 h p.i and reconstructed using the OS-EM algorithm, incorporating scatter, attenuation, collimator-detector response, septal scatter and penetration corrections. MC voxel-based absorbed dose rate calculations used two image sets, (i) the activity distribution represented by the SPECT images and (ii) the activity distribution from the SPECT images distributed uniformly within the volume of interest. Mean absorbed doses were calculated considering photon and charged particle emissions, and beta emissions only. True absorbed doses were calculated by MC voxel-based dosimetry of the known activity distributions for reference.ResultsConsidering photon and charged particle emissions, mean absorbed dose accuracies across all three radionuclide-collimator combinations of 3.8 ± 5.5% and 0.1 ± 0.9% (liver), 5.2 ± 10.0% and 4.3 ± 1.7% (3.0 cm tumour) and 15.0 ± 5.8% and 2.6 ± 0.6% (5.0 cm tumour) were obtained for image set (i) and (ii) respectively. Considering charged particle emissions, accuracies of 2.7 ± 4.1% and 5.7 ± 0.7% (liver), 3.2 ± 10.2% and 9.1 ± 1.7% (3.0 cm tumour) and 13.6 ± 5.7% and 7.0 ± 0.6% (5.0 cm tumour) were obtained for image set (i) and (ii) respectively.ConclusionThe hybrid WB planar-SPECT/CT method proved accurate for I-131-mIBG dosimetry, suggesting its potential for personalized treatment planning.

A scan-specific quality control acquisition for clinical whole-body (WB) MRI protocols

Objective. Image quality in whole-body MRI (WB-MRI) may be degraded by faulty radiofrequency (RF) coil elements or mispositioning of the coil arrays. Phantom-based quality control (QC) is used to identify broken RF coil elements but the frequency of these acquisitions is limited by scanner and staff availability. This work aimed to develop a scan-specific QC acquisition and processing pipeline to detect broken RF coil elements, which is sufficiently rapid to be added to the clinical WB-MRI protocol. The purpose of this is to improve the quality of WB-MRI by reducing the number of patient examinations conducted with suboptimal equipment. Approach. A rapid acquisition (14 s additional acquisition time per imaging station) was developed that identifies broken RF coil elements by acquiring images from each individual coil element and using the integral body coil. This acquisition was added to one centre’s clinical WB-MRI protocol for one year (892 examinations) to evaluate the effect of this scan-specific QC. To demonstrate applicability in multi-centre imaging trials, the technique was also implemented on scanners from three manufacturers. Main results. Over the course of the study RF coil elements were flagged as potentially broken on five occasions, with the faults confirmed in four of those cases. The method had a precision of 80% and a recall of 100% for detecting faulty RF coil elements. The coil array positioning measurements were consistent across scanners and have been used to define the expected variation in signal. Significance. The technique demonstrated here can identify faulty RF coil elements and positioning errors and is a practical addition to the clinical WB-MRI protocol. This approach was fully implemented on systems from two manufacturers and partially implemented on a third. It has potential to reduce the number of clinical examinations conducted with suboptimal hardware and improve image quality across multi-centre studies.

Predictive value of baseline 68Ga-FAPI PET/CT in the first-line therapy of pancreatic ductal adenocarcinoma (PDAC).

e16300 Background: This study aimed to explore whether parameters from the baseline 68Ga-fibroblast activating protein (FAP) inhibitor (FAPI) PET/CT could predict outcomes in PDAC patients receiving first-line treatment based on a Phase II clinical trial (previously reported in 2023 ASCO, abstr 4142 and 2024 ASCO-GI, abstr 671). Methods: Patients underwent 68Ga-FAPI PET/CT scan before the first dose of first-line treatment of NASCA (nab-paclitaxel, S-1, surufatinib, and camrelizumab) or GnP (nab-paclitaxel and gemcitabine) regimen were enrolled. The parameters of 68Ga-FAPI-04 PET/CT, including SUVmax, SUVmean, target-to-background ratio (TBR) (background including liver, muscle, and blood pool), and FAP expression tumor volume (FTV) of each tumor lesion, were recorded. The highest SUVmax, SUVmean and TBR (H-SUVmax, H-SUVmean, H-TBR), and summed FTV in each region (primary tumor, liver, peritoneal, lymph nodes, lung and bone) and whole body (WB) were also evaluated. Results: From January 2022 to July 2023, a total of 28 out of 42 patients were enrolled. Nineteen patients had received the NASCA regimen, and 9 patients had received GnP regimen. The SUVmax of primary site and metastatic sites were 16.46 (7.56-28.03) and 7.83 (2.13-19.22), respectively. The SUVmean of primary site and metastatic sites were 9.24 (4.05-14.99) and 4.63 (1.44-11.25), respectively. Both the SUVmax and SUVmean of primary site were significantly higher than that of metastatic sites (P &lt; 0.001). 68Ga-FAPI PET/CT showed higher sensitivity in detecting metastases than CT/MRI, especially peritoneal metastases. Only 30% (3/10) of patients were diagnosed with peritoneal metastases by CT/MRI. The ROC curve and AUC for the H-SUVmax, H-SUVmean, and summed FTV in WB or each region were evaluated by separating patients into responders and non-responders. H-SUVmax-WB had the highest AUC for predicting treatment response with a cut-off value of 18.2. Patients with H-SUVmax-WB below 18.2 had significantly longer progeression-free survival (PFS) than those above [8.8 months vs 3.8 months, P = 0.026, HR = 0.30, 95%CI (0.10-0.87)]. However, H-SUVmax-WB was not a prognostic factor (P = 0.292). Among H-TBRblood, TBRmuscle and TBRliver, H-TBRblood-WB (25.9 as the cut-off) was the most pronounced predictive (P = 0.001) and prognostic factor (P = 0.039). The trend of differences in PFS continue exists both in NASCA (p = 0.047) and GnP group (p = 0.018). The multivariable analysis revealed that H-TBRblood-WB (P = 0.026) and liver meatastases (P = 0.026) were independent predictive factors. Conclusions: The highest TBRblood of tumor lesions on 68Ga-FAPI PET/CT was associated with poor response in first-line treatment of PDAC. The utility of 68Ga FAPI PET/CT before treatment could reflect the tumor burden and may predict the response of therapy. For those with high uptake of FAPI, therapy targeting FAP might have a promising future.

127 Utilizing predictive models for bone mineral content and bone mineral density as a tool to assess dietary phosphorous

Abstract Dietary phosphorous is a necessary nutrient for bone development in pigs at all stages of its growing. Deficiencies in phosphorous decrease bone mineral content (BMC) and bone mineral density (BMD) and may be a causative of lameness. However, the normal range expected in whole body (WB) and individual bones for BMC and BMD in commercial pigs has been poorly defined. Therefore, our objectives were to 1) model normal WB bone density at multiple timepoints in wean to finish pigs, and 2) determine the extent to which individual bone (femur and 3rd metatarsal) BMC and BMD could predict WB BMC and BMD. Mixed sex pigs [Camborough (1050) x 337, PIC] were utilized and included freshly weaned ~21 d (n = 8), ~44 d of age (n = 24), ~84 d of age (n = 24) and ~154 d of age (n = 24). Pigs were individually penned. Excluding weaning age, at each age group pigs were randomly assigned to diets adequate, marginally deficient, or deficient in available phosphorus (avP) and fed for 3, 4, and 6 wk (age group 44, 84, 154, respectively). Within each age group, diets were formulated to meet nutrient and energy requirements except for avP and pigs fed ad libitum. On-test and off-test body weight (BW) and feed intake and gain to feed ratio were assessed for each age group. At the end of each feeding period, all pigs were euthanized and WB, femur (F) and 3rd metatarsal (M) BMC and BMD determined by dual X-ray absorptiometry (DXA). Data were analyzed using linear and generalized additive models that predicted response variables (BMC or BMD) as a function of BW or age. Only pigs fed adequate avP diets were used in the model fit. Pigs fed adequate avP diets increased BMD with age (0.22, 0.42, 0.84 and 1.10 g/cm2, days of age 21, 44, 84 and 154 respectively, P &amp;lt; 0.001). Within day of age 84, marginally and deficient avP diets reduced BMC and BMD by 21 to 41% (P = 0.002) and 12 to 25% (P = 0.006), respectively. Within day of age 154, marginally and deficient avP diets reduced BMC and BMD by 9% (P = 0.05) and 6 to 8% (P = 0.06), respectively. Body weight record and individual bone (F and M) BMC and BMD from pigs fed deficient avP diets were used to predict WB BMC and BMD and the mean square error of prediction was selected as a criterion to evaluate the ability of the models to detect these inadequately fed pigs. Using the selected models, pigs fed nutritionally deficient diets were detected due to 2- to 7-fold increase in MSE of predicted WBMD or WBMC compared with pigs fed adequate diets. These models can be used to assess bone development and strength in growing pigs and to infer the adequacy of avP level supplied in their diets.

Predictive factors of bone strength variation in adolescent girls according to body composition.

This study examined correlations among anthropometric parameters, body composition, bone parameters and predictive factors of bone mass in adolescent girls with different body fat percentages (%fat). A total of 129 females aged 15-18 years were categorized into 3 groups using %fat-for-age at the 50th and 95th percentiles as cutoff points (normal, over, and excess %fat groups). We recorded anthropometric data and measured the speed of sound at the tibia and radius using quantitative ultrasound. Dual-energy x-ray absorptiometry (DXA) was used to measure body composition and bone parameters, including bone mineral density (BMD), bone mineral content (BMC), and the BMD-z-score (z-score) in the lumbar spine (LS) and whole body (WB). These parameters were compared among the 3 groups using bivariate and multivariate correlation analyses. There were strong correlations among all anthropometric parameters, body composition, and DXA in the over %fat group. Lean parameters strongly correlated with LS and WB in the normal %fat group, whereas both lean mass (LM) and fat mass (FM) were positively correlated with BMC in the excess %fat group. The predictive factors of bone mass differed among the groups, as follows: lean body mass was predictive of BMD and BMC at both sites in the normal and over %fat groups; LM and body weight were predictive of LS-BMC and WB-bones, respectively, in the over %fat group; and FM was predictive of WB-bones in the excess %fat group. Body fat and waist circumference were negative predictors of bone mass. Predictive factors of bone strength appear to depend on the amount of body fat in adolescent girls.

Low-dose and standard-dose whole-body [18F]FDG-PET/CT imaging: implications for healthy controls and lung cancer patients

Aim: High-sensitivity hybrid positron emission tomography (PET) imaging using advanced whole-body (WB) or total-body PET/computed tomography (CT) systems permits reducing injected tracer activity while preserving diagnostic quality. Such approaches are promising for healthy control studies or exploring inter-organ communication in systemic diseases. This study assessed test/retest variations in the fluoro-2-deoxy-D-glucose (FDG) uptake in key organs from low-dose (LD) and standard-dose (STD) [18F]FDG-PET/CT imaging protocols in healthy controls and lung cancer patients.Methods: A total of 19 healthy controls (19–62 years, 46–104 kg, 10 M/9 F) and 7 lung cancer patients (47–77 years, 50–88 kg, 4 M/3 F) underwent [18F]FDG-PET/CT imaging. All subjects were first injected (“test,” LD) with 28 ± 2 MBq FDG and underwent a dynamic (0–67 min post-injection) WB imaging protocol with LD-CT. Then, 90 min post-LD injection, the subjects were repositioned and injected with 275 ± 16 MBq FDG (“retest,” STD). Second LD-CT and STD-CT scans were acquired for healthy controls and patients, respectively. Static images (55–67 min post-injection) were considered for subsequent analysis. The CT images were used to automatically segment the target volumes of interest. Standardized uptake values normalized to the body weight (SUVBW) were extracted for each volume of interest. The mean SUVBW were compared for both LD/STD conditions with paired t-tests. In patients, FDG-avid lesions were manually delineated on LD and STD static images. Effective dose levels were estimated from both the CT and PET acquisitions.Results: Organ-based mean SUVBW were similar between the LD and STD (mean %difference ≤5%) in both healthy controls and cancer patients, except in the heart. Intra-control test/retest variability was significant in the brain, heart, and skeletal muscle (p &amp;lt; 0.05). While 17 lesions were delineated on the STD images of the patients, only 10/17 lesions were identified on the LD images due to increased image noise. Lesion-based mean SUVBW were similar between LD and STD acquisitions (p = 0.49, %difference = 10%). In patients, the effective doses were (1.9 ± 0.2) mSv (LD-CT), (16.6 ± 5.4) mSv (STD-CT), (0.5 ± 0.1) mSv (LD-PET), and (4.6 ± 0.3) mSv (STD-PET).Conclusion: LD and STD [18F]FDG injections in healthy controls and lung cancer patients yielded comparable mean SUVBW, except in the heart. Dose levels may be reduced for [18F]FDG-PET imaging without a loss in mean SUVBW accuracy, promoting LD-PET/CT protocols for studying multi-organ metabolic patterns. In oncology patients, this approach may be hindered by a lower diagnostic quality in the presence of significant noise.

Dynamic whole-body [18F]FES PET/CT increases lesion visibility in patients with metastatic breast cancer

BackgroundCorrect classification of estrogen receptor (ER) status is essential for prognosis and treatment planning in patients with breast cancer (BC). Therefore, it is recommended to sample tumor tissue from an accessible metastasis. However, ER expression can show intra- and intertumoral heterogeneity. 16α-[18F]fluoroestradiol ([18F]FES) Positron Emission Tomography/Computed Tomography (PET/CT) allows noninvasive whole-body (WB) identification of ER distribution and is usually performed as a single static image 60 min after radiotracer injection. Using dynamic whole-body (D-WB) PET imaging, we examine [18F]FES kinetics and explore whether Patlak parametric images (Ki\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$${K}_{i}$$\\end{document}) are quantitative and improve lesion visibility.ResultsThis prospective study included eight patients with metastatic ER-positive BC scanned using a D-WB PET acquisition protocol. The kinetics of [18F]FES were best characterized by the irreversible two-tissue compartment model in tumor lesions and in the majority of organ tissues. Ki\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$${K}_{i}$$\\end{document} values from Patlak parametric images correlated with Ki\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$${K}_{i}$$\\end{document} values from the full kinetic analysis, r2 = 0.77, and with the semiquantitative mean standardized uptake value (SUVmean), r2 = 0.91. Furthermore, parametric Ki\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$${K}_{i}$$\\end{document} images had the highest target-to-background ratio (TBR) in 162/164 metastatic lesions and the highest contrast-to-noise ratio (CNR) in 99/164 lesions compared to conventional SUV images. TBR was 2.45 (95% confidence interval (CI): 2.25–2.68) and CNR 1.17 (95% CI: 1.08–1.26) times higher in Ki\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$${K}_{i}$$\\end{document} images compared to SUV images. These quantitative differences were seen as reduced background activity in the Ki\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$${K}_{i}$$\\end{document} images.Conclusion[18F]FES uptake is best described by an irreversible two-tissue compartment model. D-WB [18F]FES PET/CT scans can be used for direct reconstruction of parametric Ki\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$${K}_{i}$$\\end{document} images, with superior lesion visibility and Ki\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$${K}_{i}$$\\end{document} values comparable to Ki\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$${K}_{i}$$\\end{document} values found from full kinetic analyses. This may aid correct ER classification and treatment decisions.Trial registration ClinicalTrials.gov: NCT04150731, https://clinicaltrials.gov/study/NCT04150731

Optimisation of the bone single photon emission computed tomography in oncology patients

Introduction: The introduction of hybrid imaging systems such as Single Photon Emission Computed Tomography/Computed Tomography (SPECT/CT) has completely changed the scanning procedure of conventional diagnostic nuclear medicine protocols. Modern bone scintigraphy protocols include SUV quanitification and Whole Body (WB) SPECT/CT scanning modality. The major limitation of these new technologies is relatively long scanning time. New detector systems with modern reconstruction softwares have been developed for fast scanning SPECT protocolos. These new technologies can produce images of reduced acquisition with same quality as full scanning acquisition. As a result new studies suggest that planar WB scintigraphy should be replaced with WB SPECT/CT. Methods: One hundred oncology patients performed SPECT/CT as a part as their clinical follow-up. Three different scanning and three reconstruction protocols have been evaluated. Two nuclear medicine physicians evaluated with Likert scale image sharpness, lesion visibility, and lesion background detectability. The overall image quality was determined as the sum of these three parameters. Results: In terms of scan duration reduction on image quality, Volumetrix Evolution for Bone performed during ultra-fast SPECT acquisition achieved the highest score, which is superior compared to the standard SPECT acquisition protocol. The overall image quality was the best with the Volumetrix MI Evolution for Bone protocol for ultra-fast acquisition Conclusion: The Evolution for Bone protocol for ultra-fast acquisition showed best results compared to other protocols. The adoption of new acquisition SPECT protocol may offer more comfortable exams, resulting in higher patient satisfaction. The implementation of this new protocol can lead to an improvement in SPECT sensitivity, primarily due to the reduction of SPECT motion artifacts.

Clinical Internal Dosimetry and Biodistribution of 177 Lu-DOTA-Trastuzumab in HER2-Positive Metastatic and Locally Advanced Breast Carcinoma.

The aim of this study was to assess the biodistribution and dosimetry of 177 Lu-DOTA-trastuzumab in patients with HER2-positive breast carcinoma using whole-body (WB) planar imaging at multiple time points. This study was a prospective evaluation of HER2-positive metastatic/locally advanced breast carcinoma patients who underwent gamma camera imaging for dosimetry and biodistribution studies by using 177 Lu-DOTA-trastuzumab. The standard diagnostic dosimetry protocol was followed, which included cold trastuzumab injection followed by in-house produced 177 Lu-DOTA-trastuzumab. Serial WB planar images (anterior and posterior) were obtained on gamma camera after the infusion of 177 Lu-DOTA-trastuzumab at multiple time points. Whole-body and organ regions of interest were drawn, and the numbers of disintegrations were obtained. The mean absorbed doses for the liver, spleen, kidneys, heart, red marrow, and tumor were obtained from OLINDA EXM v2.1.1 and ORIGIN software. The study included a cohort of 21 female breast carcinoma patients. Tracer activity ( 177 Lu-DOTA-trastuzumab) was noted in the physiological organs such as the liver, spleen, kidneys, heart, as well as in the tumors. On visual analysis of 177 Lu-DOTA-trastuzumab biodistribution, the liver activity showed gradual clearance over time, and although spleen was comparatively faintly visualized than liver and similarly, kidneys were faintly visualized suggestive of the alternate route of tracer excretion. The maximum number of patients (n = 12) showed 2 components of clearance, namely, fast and slow. The average effective half-life of all the patients (including single and 2 components of clearance) was 106.25 ± 22.14 hours (84.11-128.39 hours). The mean absorbed dose for the liver, spleen, kidneys, heart, whole body, and red marrow was 1.0702 ± 0.731, 1.4114 ± 0.462, 1.4232 ± 0.364, 1.4719 ± 0.602, 0.2412 ± 0.0295, and 0.1485 ± 0.0213 mGy/MBq, respectively, by OLINDA EXM and 0.5741 ± 0.333, 0.8096 ± 0.224, 0.7943 ± 0.235, 1.8971 ± 0.713, and 0.09619 ± 0.0144 for liver, spleen, kidneys, heart and whole body respectively by ORIGIN. The absorbed radiation dose for tumor was 1.94E+2 by OLINDA EXM software and 1.78E+2 by ORIGIN software. In this study, during and after infusion of 177 Lu-DOTA-trastuzumab, no major adverse effects were noted in any patient except 1 patient who had grade 1 nausea and managed conservatively by antiemetic drug. The results of our study demonstrated expected and favorable biodistribution and dosimetry with 177 Lu-DOTA-trastuzumab in HER2-positive breast carcinoma patients. We noticed the mean absorbed dose to the normal organs within the limits of maximum tolerable dose, and also tumor dose was higher than the normal liver dose. Therefore, we conclude that 177 Lu-DOTA-trastuzumab radioimmunotherapy is feasible and a safe treatment option for treating HER2-positive breast carcinoma patients.

Low- and high-volume disease in mHSPC, from CHAARTED to PSMA-PET: An international multicenter retrospective study.

44 Background: High-volume disease (HVD) and low-volume disease (LVD) definitions are based on conventional imaging (CI = CT + bone scan (BS)) according to CHAARTED. Volume of disease is associated with overall survival and used for treatment decisions in mHSPC patients. It remains unknown how these definitions transfer to PSMA-PET. Methods: mHSPC patients from 4 international sites who underwent PSMA-PET+BS within a maximum time interval of 100 days and without any new treatment in between were retrospectively included. CHAARTED stratification into HVD/LVD was applied to BS, CT, MRI and PSMA-PET. HVD was defined by the presence of visceral metastases and/or ≥ 4 bone metastases (with ≥ 1 beyond spine / pelvis). EXINIbone 3.4 (EXINI Diagnostics) was used for the automated bone scan index (aBSI) and the number/localization of lesions on BS. The whole-body (WB) PSMA-PET positive tumor volume (PSMA-TV) was obtained using a semi-automatic thresholding method on Affinity 3.0.2 (Hermes Medical Solutions). Results: Fifty-sevenpairs of PSMA-PET/CT+BS were included (median PSA 226.0 (0.2–2840.0 ng/ml). Based on CI, 16/57 patients had CI-HVD (28.1%) and 41/57 CI-LVD (71.9%). Based on PSMA-PET, 25/57 patients had PSMA-HVD (43.9%) and 19/57 PSMA-LVD (33.3%), 13/57 (22.8%) patients had on PSMA-PET no PSMA-positive or only local / N1-disease. Upshift and downshift from CI to PSMA-PET occurred in 22/57 (38.6%): 9/57 (22.0%) patients were upstaged and 13/57 (22.8%) were downstaged by PSMA-PET. The downshifted patients had no PSMA-PET-positive lesion or only in the prostate fossa while CI was M1 disease. The mean WB-PSMA-TV and aBSI were for CI-HVD was 778.2 ml (0.3–3734.0) and 3.8% (0–11.7), for CI-LVD 51.6 ml (0–228.0) and 0.1% (0–0.6), for PSMA-HVD 573.7 ml (7.9–3734.0) and 2.6% (0–11.7) and for PSMA-LVD, 49.4 ml (1.6–228.0) and 0.1% (0–0.6), respectively. Conclusions: Stage migration between LVD and HVD from CI to PSMA-PET occurs both by up- and downstaging. HVD/LVD based on PSMA PET/CT should be redefined based on patients’ outcome.

Association of serum trimethylamine N-oxide levels and bone mineral density in type 2 diabetes mellitus.

The relationship between trimethylamine N-oxide (TMAO) and bone mineral density (BMD) in type 2 diabetes mellitus (T2DM) is unclear. We explore the relationship between TMAO levels and BMD in T2DM. This is a cross-sectional study. 254 T2DM patients were enrolled and divided into three groups by TMAO tertiles, and the clinical data were collected. BMD was determined by dual-energy X-ray absorptiometry (DXA) and serum TMAO levels was determined by stable isotope dilution high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS). Patients in the highest tertile of TMAO levels (TMAO > 6.72 μmol/L) showed relatively low BMD and a higher number of fracture history, osteoporosis (OP) than those in the lower tertiles. Spearman correlation analysis showed that serum TMAO was negatively correlated with BMD of whole body (WB), lumbar spine (LS) and femoral neck (FN), while TMAO was positive correlated with osteoporotic fracture (p < 0.05). Logistic regression models showed that TMAO was an independent influencing factor of fracture history after adjusting for confounders in TMAO > 6.72 μmol/L group. There is a significant linear correlation between TMAO levels and BMD in T2DM patients. Especially in TMAO > 6.72 μmol/L group, TMAO was negatively correlated with WB, LS, and FN BMD, and was positive correlated with osteoporotic fracture in T2DM patients. The findings suggest that elevated TMAO levels are associated with OP and osteoporotic fracture in T2DM patients.