Optimization-derived blood input function using a kernel method and its evaluation with total-body PET for brain parametric imaging.

Dynamic PET allows quantification of physiological parameters through tracer kinetic modeling. For dynamic imaging of brain or head and neck cancer on conventional PET scanners with a short axial field of view, the image-derived input function (ID-IF) from intracranial blood vessels such as the carotid artery (CA) suffers from severe partial volume effects. Alternatively, optimization-derived input function (OD-IF) by the simultaneous estimation (SIME) method does not rely on an ID-IF but derives the input function directly from the data. However, the optimization problem is often highly ill-posed. We proposed a new method that combines the ideas of OD-IF and ID-IF together through a kernel framework. While evaluation of such a method is challenging in human subjects, we used the uEXPLORER total-body PET system that covers major blood pools to provide a reference for validation. METHODS: The conventional SIME approach estimates an input function using a joint estimation together with kinetic parameters by fitting time activity curves from multiple regions of interests (ROIs). The input function is commonly parameterized with a highly nonlinear model which is difficult to estimate. The proposed kernel SIME method exploits the CA ID-IF as a priori information via a kernel representation to stabilize the SIME approach. The unknown parameters are linear and thus easier to estimate. The proposed method was evaluated using 18F-fluorodeoxyglucose studies with both computer simulations and 20 human-subject scans acquired on the uEXPLORER scanner. The effect of the number of ROIs on kernel SIME was also explored. RESULTS: The estimated OD-IF by kernel SIME showed a good match with the reference input function and provided more accurate estimation of kinetic parameters for both simulation and human-subject data. The kernel SIME led to the highest correlation coefficient (R = 0.97) and the lowest mean absolute error (MAE = 10.5 %) compared to using the CA ID-IF (R = 0.86, MAE = 108.2 %) and conventional SIME (R = 0.57, MAE = 78.7 %) in the human-subject evaluation. Adding more ROIs improved the overall performance of the kernel SIME method. CONCLUSION: The proposed kernel SIME method shows promise to provide an accurate estimation of the blood input function and kinetic parameters for brain PET parametric imaging.

High-standard predictive equations for estimating body composition using bioelectrical impedance analysis: a systematic review.

The appropriate use of predictive equations in estimating body composition through bioelectrical impedance analysis (BIA) depends on the device used and the subject's age, geographical ancestry, healthy status, physical activity level and sex. However, the presence of many isolated predictive equations in the literature makes the correct choice challenging, since the user may not distinguish its appropriateness. Therefore, the present systematic review aimed to classify each predictive equation in accordance with the independent parameters used. Sixty-four studies published between 1988 and 2023 were identified through a systematic search of international electronic databases. We included studies providing predictive equations derived from criterion methods, such as multi-compartment models for fat, fat-free and lean soft mass, dilution techniques for total-body water and extracellular water, total-body potassium for body cell mass, and magnetic resonance imaging or computerized tomography for skeletal muscle mass. The studies were excluded if non-criterion methods were employed or if the developed predictive equations involved mixed populations without specific codes or variables in the regression model. A total of 106 predictive equations were retrieved; 86 predictive equations were based on foot-to-hand and 20 on segmental technology, with no equations used the hand-to-hand and leg-to-leg. Classifying the subject's characteristics, 19 were for underaged, 26 for adults, 19 for athletes, 26 for elderly and 16 for individuals with diseases, encompassing both sexes. Practitioners now have an updated list of predictive equations for assessing body composition using BIA. Researchers are encouraged to generate novel predictive equations for scenarios not covered by the current literature.Registration code in PROSPERO: CRD42023467894.

Comparison of parametric imaging and SUV imaging with [68 Ga]Ga-PSMA-11 using dynamic total-body PET/CT in prostate cancer.

PURPOSE: Standardized uptake value (SUV) has been prevalently used to measure [68 Ga]Ga-PSMA-11 activity in prostate cancer, but it is susceptible to multiple factors. Parametric imaging allows for absolute quantification of tracer uptake and provides a better diagnostic accuracy that is crucial for lesion detection. However, the clinical significance of total-body parametric imaging of [68 Ga]Ga-PSMA-11 remains to be fully assessed. Therefore, the aim of our study is to delve into the diagnostic implications of total-body parametric imaging of [68 Ga]Ga-PSMA-11 PET/CT for patients with prostate cancer. METHODS: Twenty prostate cancer patients were included and underwent a dynamic total-body [68 Ga]Ga-PSMA-11 PET/CT scan. An irreversible two-tissue compartment model (2T3k) was fitted for each tissue time-to-activity curve, and the net influx rate (Ki) was obtained. The image quality and semi-quantitative analysis of lesion-to-background ratio (LBR), signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR) were compared between parametric images and SUV images. RESULTS: Kinetic modeling using 2T3k demonstrated favorable model fitting in both normal organs and lesions. All of the lesions detected on SUV images (55-60 min) could be detected on Ki images. The correlation between Ki, SUVmean, and SUVmax in both normal organs and pathological lesions was found to be positive and statistically significant. Conversely, a moderate positive correlations were found between Ki and K1 (R = 0.69, P < 0.001; R = 0.61, P < 0.001) and Ki and k3 (R = 0.69, P < 0.001; R = 0.62, P < 0.001), in normal organs and pathological lesions, respectively. Visual assessment in Ki images showed less image noise and higher lesions conspicuity compared to SUV images. Ki image-derived LBR, SNR, and CBR of pathological lesions including primary tumors (PTs), lymph node metastases (LNMs) and bone metastases (BMs), exhibited remarkably higher folds (1.4-3.6 folds) compared to those derived from SUV of corresponding lesions. CONCLUSIONS: Total-body parametric imaging of [68 Ga]Ga-PSMA-11 enhanced lesion contrast and improved lesion detectability compared to SUV images. This may potentially serve as an imaging biomarker and theranostic tool for precise diagnosis and treatment evaluation in prostate cancer patients.

Assessing dynamic metabolic heterogeneity in prostate cancer patients via total-body [68Ga]Ga-PSMA-11 PET/CT imaging: quantitative analysis of [68Ga]Ga-PSMA-11 uptake in pathological lesions and normal organs.

PURPOSE: This study aimed to quantitatively assess [68Ga]Ga-PSMA-11 uptake in pathological lesions and normal organs in prostate cancer using the total-body [68Ga]Ga-PSMA-11 PET/CT and to characterize the dynamic metabolic heterogeneity of prostate cancer. METHODS: Dynamic total-body [68Ga]Ga-PSMA-11 PET/CT scans were performed on ten prostate cancer patients. Manual delineation of volume-of-interests (VOIs) was performed on multiple normal organs displaying high [68Ga]Ga-PSMA-11 uptake, as well as pathological lesions. Time-to-activity curves (TACs) were generated, and the four compartment models including one-tissue compartmental model (1T1k), reversible one-tissue compartmental model (1T2k), irreversible two-tissue compartment model (2T3k) and reversible two-tissue compartmental model (2T4k) were fitted to each tissue TAC. Various rate constants, including K1 (forward transport rate from plasma to the reversible compartment), k2 (reverse transport rate from the reversible compartment to plasma), k3 (tracer binding on the PSMA-receptor and its internalization), k4 (the externalization rate of the tracer) and Ki (net influx rate), were obtained. The selection of the optimal model for describing the uptake of both lesions and normal organs was determined using the Akaike information criteria (AIC). Receiver operating characteristic (ROC) curve analysis was performed to determine the cut-off values for differentiating physiological and pathological [68Ga]Ga-PSMA-11 uptake. RESULTS: Both 1T1k and 1T2k models showed relatively high AIC values compared to the 2T3k and 2T4k models in both pathological lesions and normal organs. The kinetic behavior of pathological lesions was better described by the 2T3k model compared to the 2T4k model, while the normal organs were better described by the 2T4k model. Significant variations in kinetic metrics, such as K1, k2, and k3, and Ki, were observed among normal organs with high [68Ga]Ga-PSMA-11 uptake and pathological lesions. The high Ki value in normal organs was primarily determined by elevated K1 and low k3, rather than k2. Conversely, the high Ki value in pathological lesions, ranking second to the kidney and similar to salivary glands and spleen, was predominantly determined by the highest k3 value. Notably, k3 exhibited the highest performance in distinguishing between physiological and pathological [68Ga]Ga-PSMA-11 uptake, with an area under the curve (AUC) of 0.844 (95% CI, 0.773-0.915), sensitivity of 82.9%, and specificity of 74.1%. The k3 values showed better performance than SUVmean (AUC, 0.659), SUVmax (AUC, 0.637), and other kinetic parameter including K1 (AUC, 0.604), k2 (AUC, 0.634), and Ki (AUC, 0.651). CONCLUSIONS: Significant discrepancies in kinetic metrics were detected between pathological lesions and normal organs, despite their shared high uptake of [68Ga]Ga-PSMA-11. Notably, the k3 value exhibits a noteworthy capability to distinguish between pathological lesions and normal organs with elevated [68Ga]Ga-PSMA-11 uptake. This discovery implies that k3 holds promise as a prospective imaging biomarker for distinguishing between pathologic and non-specific [68Ga]Ga-PSMA-11 uptake in patients with prostate cancer.

Sedation-free pediatric [18F]FDG imaging on totalbody PET/CT with the assistance of artificial intelligence.

PURPOSE: While sedation is routinely used in pediatric PET examinations to preserve diagnostic quality, it may result in side effects and may affect the radiotracer's biodistribution. This study aims to investigate the feasibility of sedation-free pediatric PET imaging using ultra-fast total-body (TB) PET scanners and deep learning (DL)-based attenuation and scatter correction (ASC). METHODS: This retrospective study included TB PET (uExplorer) imaging of 35 sedated pediatric patients under four years old to determine the minimum effective scanning time. A DL-based ASC method was applied to enhance PET quantification. Both quantitative and qualitative assessments were conducted to evaluate the image quality of ultra-fast DL-ASC PET. Five non-sedated pediatric patients were subsequently used to validate the proposed approach. RESULTS: Comparisons between standard 300-second and ultra-fast 15-second imaging, CT-ASC and DL-ASC ultra-fast 15-second images, as well as DL-ASC ultra-fast 15-second images in non-sedated and sedated patients, showed no significant differences in qualitative scoring, lesion detectability, and quantitative Standard Uptake Value (SUV) (P = ns). CONCLUSIONS: This study demonstrates that pediatric PET imaging can be effectively performed without sedation by combining ultra-fast imaging techniques with a DL-based ASC. This advancement in sedation-free ultra-fast PET imaging holds potential for broader clinical adoption.

The superior detection rate of total-body [68Ga]Ga-PSMA-11 PET/CT compared to short axial field-of-view [68Ga]Ga-PSMA-11 PET/CT for early recurrent prostate cancer patients with PSA < 0.2 ng/mL after radical prostatectomy.

BACKGROUND AND PURPOSE: [68Ga]Ga-PSMA PET imaging has been extensively utilized for the detection of biochemical recurrence (BCR) in prostate cancer. However, the detection rate declines to merely 10-40% when PSA levels are < 0.2 ng/mL employing short axial field-of-view (SAFOV) PET. Prior studies exhibited superior detection rates with total-body [68Ga]Ga-PSMA-11 PET compared to SAFOV [68Ga]Ga-PSMA-11 PET in BCR patients with PSA > 0.2 ng/mL. Nevertheless, the diagnostic utility of total-body [68Ga]Ga-PSMA-11 PET for BCR patients when PSA is < 0.2 ng/mL remains unclear. This study aimed to assess whether total-body [68Ga]Ga-PSMA-11 PET/CT could improve the detection rate compared to SAFOV [68Ga]Ga-PSMA-11 PET/CT in BCR patients with PSA < 0.2 ng/mL. METHODS: Eighty BCR patients with PSA < 0.2 ng/mL underwent total-body [68Ga]Ga-PSMA-11 PET/CT. These patients were matched by baseline qualities to another 80 patients who received SAFOV [68Ga]Ga-PSMA-11 PET/CT. The detection rates of total-body [68Ga]Ga-PSMA-11 PET/CT and SAFOV [68Ga]Ga-PSMA-11 PET/CT were compared utilizing a chi-square test and stratified analysis. Image quality of total-body [68Ga]Ga-PSMA PET/CT and SAFOV [68Ga]Ga-PSMA-11 PET/CT was assessed based on subjective scoring and objective parameters. The objective parameters measured were SUVmax, SUVmean, standard deviation (SD) of SUV, and signal-to-noise ratio (SNR) of liver and gluteus maximus. RESULTS: The image quality of total-body [68Ga]Ga-PSMA PET/CT was superior to that of SAFOV [68Ga]Ga-PSMA-11 PET/CT in both early and delayed scans. The detection rate of total-body [68Ga]Ga-PSMA PET/CT for BCR patients with PSA < 0.2 ng/mL was significantly higher than that of SAFOV [68Ga]Ga-PSMA-11 PET/CT (73.75% vs. 43.75%, P < 0.001). Total-body [68Ga]Ga-PSMA PET/CT resulted in noteworthy modifications to the treatment regimen when contrasted with SAFOV [68Ga]Ga-PSMA-11 PET/CT. CONCLUSIONS: In BCR patients with PSA < 0.2 ng/mL, total-body [68Ga]Ga-PSMA-11 PET/CT not only demonstrated a significantly higher detection rate compared to SAFOV [68Ga]Ga-PSMA-11 PET/CT but also led to significant alterations in treatment regimens.

Assessment of image-derived input functions from small vessels for patlak parametric imaging using total-body PET/CT.

PURPOSE: The image-derived input function (IDIF) from the descending aorta has demonstrated performance comparable to arterial blood sampling while avoiding its invasive nature in parametric imaging. However, in conventional PET, large vessels may not always be within the imaging field of view (FOV). This study aims to evaluate the efficacy of dynamic parametric Ki imaging using image-derived input functions (IDIFs) extracted from various arteries, facilitated by total-body PET/CT. METHOD: Twenty-three participants underwent a 60-minute total-body [18F]FDG PET scan. Data from each subject were used to reconstruct both total-body PET images and short-axis field-of-view PET images at different bed positions, each with a 25 cm axial field-of-view (AFOV). Partial volume correction (PVC) was performed using the blurred Van Cittert iterative deconvolution. IDIFs extracted from the descending aorta, carotid artery, abdominal aorta, and iliac artery were employed for Patlak analysis. The resulting Ki images were compared using quantification indicators and subjective assessment. Linear regression analysis was conducted to examine the correlation of Ki values among IDIFs in normal organ and lesion regions of interest (ROIs). RESULT: High similarities were observed in Ki images derived from the IDIFs from the descending aorta and other arteries, with a median structural similarity index measure (SSIM) above 0.98 and a median peak signal-to-noise ratio (PSNR) above 37dB. Linear regression analysis revealed strong correlations in Ki values (r² > 0.88) between the descending aorta and the three alternative vessels, with slopes of the linear fits close to 1. No significant difference in lesion detectability among IDIFs was found, as assessed visually and using metrics such as tumor-to-background ratio (TBR) and contrast-to-noise ratio (CNR) (P < 0.05). CONCLUSION: IDIFs from smaller vessels can reliably reconstruct parametric Ki images without compromising lesion detectability, providing clinically relevant information.

Optimization and impact of sensitivity mode on abbreviated scan protocols with population-based input function for parametric imaging of [18F]-FDG for a long axial FOV PET scanner.

BACKGROUND: The long axial field of view, combined with the high sensitivity of the Biograph Vision Quadra PET/CT scanner enables the precise deviation of an image derived input function (IDIF) required for parametric imaging. Traditionally, this requires an hour-long dynamic PET scan for [18F]-FDG, which can be significantly reduced by using a population-based input function (PBIF). In this study, we expand these examinations and include the scanner's ultra-high sensitivity (UHS) mode in comparison to the high sensitivity (HS) mode and evaluate the potential for further shortening of the scan time. METHODS: Patlak Ki and DV estimates were determined by the indirect and direct Patlak methods using dynamic [18F]-FDG data of 6 oncological patients with 26 lesions (0-65 min p.i.). Both sensitivity modes for different number/duration of PET data frames were compared, together with the potential of using abbreviated scan durations of 20, 15 and 10 min by using a PBIF. The differences in parametric images and tumour-to-background ratio (TBR) due to the shorter scans using the PBIF method and between the sensitivity modes were assessed. RESULTS: A difference of 3.4 ± 7.0% (Ki) and 1.2 ± 2.6% (DV) was found between both sensitivity modes using indirect Patlak and the full IDIF (0-65 min). For the abbreviated protocols and indirect Patlak, the UHS mode resulted in a lower bias and higher precision, e.g., 45-65 min p.i. 3.8 ± 4.4% (UHS) and 6.4 ± 8.9% (HS), allowing shorter scan protocols, e.g. 50-65 min p.i. 4.4 ± 11.2% (UHS) instead of 7.3 ± 20.0% (HS). The variation of Ki and DV estimates for both Patlak methods was comparable, e.g., UHS mode 3.8 ± 4.4% and 2.7 ± 3.4% (Ki) and 14.4 ± 2.7% and 18.1 ± 7.5% (DV) for indirect and direct Patlak, respectively. Only a minor impact of the number of Patlak frames was observed for both sensitivity modes and Patlak methods. The TBR obtained with direct Patlak and PBIF was not affected by the sensitivity mode, was higher than that derived from the SUV image (6.2 ± 3.1) and degraded from 20.2 ± 12.0 (20 min) to 10.6 ± 5.4 (15 min). Ki and DV estimate images showed good agreement (UHS mode, RC: 6.9 ± 2.3% (Ki), 0.1 ± 3.1% (DV), peak signal-to-noise ratio (PSNR): 64.5 ± 3.3 dB (Ki), 61.2 ± 10.6 dB (DV)) even for abbreviated scan protocols of 50-65 min p.i. CONCLUSIONS: Both sensitivity modes provide comparable results for the full 65 min dynamic scans and abbreviated scans using the direct Patlak reconstruction method, with good Ki and DV estimates for 15 min short scans. For the indirect Patlak approach the UHS mode improved the Ki estimates for the abbreviated scans.

Intelligent ultrafast total-body PET for sedation-free pediatric [18F]FDG imaging.

PURPOSE: This study aims to develop deep learning techniques on total-body PET to bolster the feasibility of sedation-free pediatric PET imaging. METHODS: A deformable 3D U-Net was developed based on 245 adult subjects with standard total-body PET imaging for the quality enhancement of simulated rapid imaging. The developed method was first tested on 16 children receiving total-body [18F]FDG PET scans with standard 300-s acquisition time with sedation. Sixteen rapid scans (acquisition time about 3 s, 6 s, 15 s, 30 s, and 75 s) were retrospectively simulated by selecting the reconstruction time window. In the end, the developed methodology was prospectively tested on five children without sedation to prove the routine feasibility. RESULTS: The approach significantly improved the subjective image quality and lesion conspicuity in abdominal and pelvic regions of the generated 6-s data. In the first test set, the proposed method enhanced the objective image quality metrics of 6-s data, such as PSNR (from 29.13 to 37.09, p < 0.01) and SSIM (from 0.906 to 0.921, p < 0.01). Furthermore, the errors of mean standardized uptake values (SUVmean) for lesions between 300-s data and 6-s data were reduced from 12.9 to 4.1% (p < 0.01), and the errors of max SUV (SUVmax) were reduced from 17.4 to 6.2% (p < 0.01). In the prospective test, radiologists reached a high degree of consistency on the clinical feasibility of the enhanced PET images. CONCLUSION: The proposed method can effectively enhance the image quality of total-body PET scanning with ultrafast acquisition time, leading to meeting clinical diagnostic requirements of lesion detectability and quantification in abdominal and pelvic regions. It has much potential to solve the dilemma of the use of sedation and long acquisition time that influence the health of pediatric patients.

Exploring the nigrostriatal and digestive interplays in Parkinson's disease using dynamic total-body [11C]CFT PET/CT.

PURPOSE: Dynamic total-body imaging enables new perspectives to investigate the potential relationship between the central and peripheral regions. Employing uEXPLORER dynamic [11C]CFT PET/CT imaging with voxel-wise simplified reference tissue model (SRTM) kinetic modeling and semi-quantitative measures, we explored how the correlation pattern between nigrostriatal and digestive regions differed between the healthy participants as controls (HC) and patients with Parkinson's disease (PD). METHODS: Eleven participants (six HCs and five PDs) underwent 75-min dynamic [11C]CFT scans on a total-body PET/CT scanner (uEXPLORER, United Imaging Healthcare) were retrospectively enrolled. Time activity curves for four nigrostriatal nuclei (caudate, putamen, pallidum, and substantia nigra) and three digestive organs (pancreas, stomach, and duodenum) were obtained. Total-body parametric images of relative transporter rate constant (R1) and distribution volume ratio (DVR) were generated using the SRTM with occipital lobe as the reference tissue and a linear regression with spatial-constraint algorithm. Standardized uptake value ratio (SUVR) at early (1-3 min, SUVREP) and late (60-75 min, SUVRLP) phases were calculated as the semi-quantitative substitutes for R1 and DVR, respectively. RESULTS: Significant differences in estimates between the HC and PD groups were identified in DVR and SUVRLP of putamen (DVR: 4.82 ± 1.58 vs. 2.58 ± 0.53; SUVRLP: 4.65 ± 1.36 vs. 2.84 ± 0.67; for HC and PD, respectively, both p < 0.05) and SUVREP of stomach (1.12 ± 0.27 vs. 2.27 ± 0.65 for HC and PD, respectively; p < 0.01). In the HC group, negative correlations were observed between stomach and substantia nigra in both the R1 and SUVREP values (r=-0.83, p < 0.05 for R1; r=-0.94, p < 0.01 for SUVREP). Positive correlations were identified between pancreas and putamen in both DVR and SUVRLP values (r = 0.94, p < 0.01 for DVR; r = 1.00, p < 0.001 for SUVRLP). By contrast, in the PD group, no correlations were found between the aforementioned target nigrostriatal and digestive areas. CONCLUSIONS: The parametric images of R1 and DVR generated from the SRTM model, along with SUVREP and SUVRLP, were proposed to quantify dynamic total-body [11C]CFT PET/CT in HC and PD groups. The distinction in correlation patterns of nigrostriatal and digestive regions between HC and PD groups identified by R1 and DVR, or SUVRs, may provide new insights into the disease mechanism.

Total-body PET/CT with half-dose [68 Ga]Ga-PSMA-11 for biochemical recurrent prostate cancer: comparable diagnostic value to short axial field-of-view PET/CT with full-dose [68 Ga]Ga-PSMA-11.

PURPOSE: The objective of this study was to evaluate the diagnostic performance and image quality of total-body positron emission tomography/computed tomography (PET/CT) imaging using a half-dose of [68 Ga]Ga-prostate specific membrane antigen ([68 Ga]Ga-PSMA) radiotracer, compared to conventional short axial field-of-view PET/CT imaging using a full dose of [68 Ga]Ga-PSMA. METHODS: This retrospective study enrolled 52 patients with biochemical recurrent (BCR) prostate cancer after radical prostatectomy who underwent total-body PET/CT with a half-dose (0.9-1.1 MBq/kg) of [68 Ga]Ga-PSMA. These patients were matched by baseline characteristics to another 52 BCR patients after prostatectomy who underwent conventional PET/CT with a full dose (1.8-2.2 MBq/kg) of [68 Ga]Ga-PSMA. The half-dose group was further divided into 5-min (G5) and 2-min (G2) acquisition subgroups. Image quality was assessed through subjective analysis using a 5-point scale and objective measurements of standard uptake value maximum (SUVmax), standard uptake value mean (SUVmean), background variation (BV) of the liver, blood pool, and parotid glands. Additionally, SUVmax and tumor-to-background ratio (TBR) were calculated for lesions. RESULTS: No significant difference in subjective image quality was found between the G2 and full-dose groups (p > 0.05). PET/CT image quality was significantly higher for the G5 versus G2 (p < 0.001) and full-dose groups (p < 0.001). TBR did not differ between the G2 and full-dose groups (4.23 ± 5.21 vs 4.22 ± 3.97, p = 0.99). Liver BV was significantly lower for G2 versus full-dose groups (0.16 ± 0.03 vs 0.20 ± 0.05, p < 0.001). CONCLUSIONS: Total-body PET/CT with a half-dose [68 Ga]Ga-PSMA yields image quality superior or comparable to that of conventional PET/CT. The utilization of total-body [68 Ga]Ga-PSMA PET/CT meets the diagnostic demands of BCR patients, particularly those who exhibit reduced tolerance to prolonged horizontal positioning and scan durations, while simultaneously reducing radiation exposure for the subjects.

Dynamic total-body PET/CT imaging with reduced acquisition time shows acceptable performance in quantification of [18F]FDG tumor kinetic metrics.

PURPOSE: To investigate the feasibility of reducing the acquisition time for continuous dynamic positron emission tomography (PET) while retaining acceptable performance in quantifying kinetic metrics of 2-[18F]-fluoro-2-deoxy-D-glucose ([18F]FDG) in tumors. METHODS: In total, 78 oncological patients underwent total-body dynamic PET imaging for ≥ 60 min, with 8, 20, and 50 patients receiving full activity (3.7 MBq/kg), half activity (1.85 MBq/kg), and ultra-low activity (0.37 MBq/kg) of [18F]FDG, respectively. The dynamic data were divided into 21-, 30-, 45- and ≥ 60-min groups. The kinetic analysis involved model fitting to derive constant rates (VB, K1 to k3, and Ki) for both tumors and normal tissues, using both reversible and irreversible two-tissue-compartment models. One-way ANOVA with repeated measures or the Freidman test compared the kinetic metrics among groups, while the Deming regression assessed the correlation of kinetic metrics among groups. RESULTS: All kinetic metrics in the 30-min and 45-min groups were statistically comparable to those in the ≥ 60-min group. The relative differences between the 30-min and ≥ 60-min groups ranged from 12.3% ± 15.1% for K1 to 29.8% ± 30.0% for VB, and those between the 45-min and ≥ 60-min groups ranged from 7.5% ± 8.7% for Ki to 24.0% ± 24.3% for VB. However, this comparability was not observed between the 21-min and ≥ 60-min groups. The significance trend of these comparisons remained consistent across different models (reversible or irreversible), administrated activity levels, and partial volume corrections for lesions. Significant correlations in tumor kinetic metrics were identified between the 30-/45-min and ≥ 60-min groups, with Deming regression slopes > 0.813. In addition, the comparability of kinetic metrics between the 30-min and ≥ 60-min groups were established for normal tissues. CONCLUSION: The acquisition time for dynamic PET imaging can be reduced to 30 min without compromising the ability to reveal tumor kinetic metrics of [18F]FDG, using the total-body PET/CT system.

The clinical acceptability of short versus long duration acquisitions for head and neck cancer using long-axial field-of-view PET/CT: a retrospective evaluation.

PURPOSE: To evaluate the utility of long duration (10 min) acquisitions compared to standard 4 min scans in the evaluation of head and neck cancer (HNC) using a long-axial field-of-view (LAFOV) system in 2-[18F]FDG PET/CT. METHODS: HNC patients undergoing LAFOV PET/CT were included retrospectively according to a predefined sample size calculation. For each acquisition, FDG avid lymph nodes (LN) which were highly probable or equivocal for malignancy were identified by two board certified nuclear medicine physicians in consensus. The aim of this study was to establish the clinical acceptability of short-duration (4 min, C40%) acquisitions compared to full-count (10 min, C100%) in terms of the detection of LN metastases in HNC. Secondary endpoints were the positive predictive value for LN status (PPV) and comparison of SUVmax at C40% and C100%. Histology reports or confirmatory imaging were the reference standard. RESULTS: A total of 1218 records were screened and target recruitment was met with n = 64 HNC patients undergoing LAFOV. Median age was 65 years (IQR: 59-73). At C40%, a total of 387 lesions were detected (highly probable LN n = 274 and equivocal n = 113. The total number of lesions detected at C100% acquisition was 439, of them 291 (66%) highly probable LN and 148 (34%) equivocal. Detection rate between the two acquisitions did not demonstrate any significant differences (Pearson's Chi-Square test, p = 0.792). Sensitivity, specificity, PPV, NPV and accuracy for C40% were 83%, 44%, 55%, 76% and 36%, whilst for C100% were 85%, 56%, 55%, 85% and 43%, respectively. The improved accuracy reached borderline significance (p = 0.057). At the ROC analysis, lower SUVmax was identified for C100% (3.5) compared to C40% (4.5). CONCLUSION: In terms of LN detection, C40% acquisitions showed no significant difference compared to the C100% acquisitions. There was some improvement for lesions detection at C100%, with a small increment in accuracy reaching borderline significance, suggestive that the higher sensitivity afforded by LAFOV might translate to improved clinical performance in some patients.

CLAG combined with total body irradiation as intensive conditioning chemotherapy prior to allogeneic hematopoietic stem cell transplantation in patients with refractory or relapsed acute myeloid leukemia.

Refractory or relapsed acute myeloid leukemia (R/R AML) remains the major challenge of AML treatment. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only valid option to achieve cure, but the prognosis is still dismal. We conducted a retrospective analysis for the feasibility of CLAG regimens (cladribine, cytarabine, and granulocyte colony-stimulating factor) combined with total body irradiation (TBI) as new intensive conditioning chemotherapy prior to HSCT in R/R AML. A total of 70 patients, including 21 primary refractory and 49 relapsed AML, were analyzed. Forty-nine (70%) patients had extramedullary diseases, and 54 (77%) patients received haploidentical transplantation. Except for one who died before white blood cell engraftment, all of the 69 evaluable patients achieved measurable residual disease (MRD) negative complete remission. The 3-year overall survival (OS) and relapse-free survival (RFS) rates were 46.0% (95% confidence interval [CI], 33.5-57.7%) and 38.5% (95%CI, 26.8-50.0%). The 1-year cumulative incidences of relapse and non-relapse mortality (NRM) were 38.6% (95%CI, 27.3-49.3%) and 11.6% (95%CI: 5.4-20.3%), respectively. The presence of chronic graft-versus-host disease (cGVHD) showed a trend to be associated with a lower risk of relapse (P = 0.054) and extramedullary diseases with a higher risk of NRM (P = 0.074). Multivariate analyses identified low leukemia burden pre-HSCT (defined as bone marrow blasts ≤ 50%) and cGVHD as independent factors associated with favorable OS and RFS. In conclusion, intensive conditioning with CLAG regimens plus TBI may be an effective and well-tolerated choice for R/R AML patients undergoing allo-HSCT.

Low dose optimization for total-body 2-[18F]FDG PET/CT imaging: a single-center study on feasibility based on body mass index stratification.

OBJECTIVES: Implementing personalization protocol in clinical routine necessitates diverse low-dose PET/CT scan protocols. This study explores the clinical feasibility of one-third (1/3) dose regimen and evaluates the diagnostic image quality and lesion detectability of BMI-based 1/3-injection doses for 2-[18F]FDG PET/CT imaging. METHODS: Seventy-four cancer patients underwent total-body 2-[18F]FDG PET/CT examination, with 37 retrospectively enrolled as full-dose group (3.7 MBq/kg) and 37 prospectively enrolled as the 1/3-dose group (1.23 MBq/kg). The 1/3-dose group was stratified by BMI, with an acquisition time of 5 min (G5), 6 min (G6), and 8 min (G8) for BMI < 25, 25 ≤ BMI ≤ 29, and BMI > 29, respectively. Image quality was subjectively and objectively assessed, and lesion detectability was quantitatively analyzed. RESULTS: Subjective assessments of 1/3-dose and full-dose PET images showed strong agreement among readers (κ > 0.88). In the 1/3-dose group, the Likert scores were above 4. G5, G6, and G8 showed comparable image quality, with G5 demonstrating higher lesion conspicuity than G6 and G8 (p = 0.045). Objective evaluation showed no significant differences in SUVmax, liver SUVmean and TBR between 1/3- and full-dose groups (p > 0.05). No statistical differences were observed in the SUVmax of primary tumor, SUVmean of liver and TBR across all BMI categories between the 1/3-dose and full-dose groups. Lesion detection rates showed no significant difference between the 1/3-dose (93.24%, 193/207) and full-dose groups (94.73%, 198/209) (p = 0.520). CONCLUSION: A BMI-stratified 1/3-dose regimen is a feasible low-dose alternative with clinically acceptable lesion detectability equivalent to full-dose protocol, potentially expanding the applicability of personalized protocols. CLINICAL RELEVANCE STATEMENT: This study demonstrated that BMI-stratified 1/3-dose regimens for [18F]FDG total-body PET/CT yielded equivalent outputs compared to the full-dose regimen, which aligns with clinical needs for personalization in dose and BMI. KEY POINTS: Currently, limited personalized low-dose total-body PET/CT protocols are available, particularly for patients with varied BMI. Reducing the radiotracer dose to 1/3 the standard demonstrated comparable image quality and lesion detectability equivalent to full dose. BMI-stratified 1/3-dose regimen is a clinically feasible low-dose alternative.

Unveiling decomposition dynamics: leveraging 3D models for advanced forensic analysis.

Forensic taphonomy, the study of post-mortem processes, is pivotal in modern forensic science. This short communication illuminates limitations in traditional 2D imaging, specifically digital photographs, within forensic taphonomy, and highlights the vast potential of 3D modeling techniques. Drawing from a recent study in Hawaii's tropical savanna, we unveil disparities between real-time observations and 2D photographs when assessing decomposition, emphasizing the importance of scoring method selection and the need to scrutinize 2D imaging's accuracy in forensic taphonomy. Conversely, 3D modeling techniques, an emerging powerhouse in forensic science, offer multidimensional data, including volume, surface area, and spatial relationships, allowing for comprehensive and precise representation of decomposition dynamics. Despite concerns about texture quality, 3D models yield objective data amenable to analysis by multiple experts, thus minimizing subjectivity and augmenting the reliability of forensic assessments. The potential for 3D modeling to bridge the gap between 2D imaging and real-time decomposition requires tailored methodologies. Future research should focus on standardizing protocols and fostering collaboration among forensic experts, technologists, and researchers to unleash 3D technology's full potential in advancing forensic taphonomy.

Incorporating intensity modulated total body irradiation into a Children's Oncology Group trial: Rationale, techniques, and safeguards.

Historically, total body irradiation (TBI) has been delivered using static, parallel opposed photon beams (2D-TBI). Recently, centers have increasingly used intensity-modulated radiation therapy (IMRT) techniques for TBI. Relative to 2D-TBI, IMRT can reduce doses to critical organs (i.e., lungs and kidneys) while delivering myeloablative doses to the rest of the body, so it may decrease the risk of toxicity while maintaining oncologic outcomes. Despite these potential benefits, delivering TBI using IMRT introduces new challenges in treatment planning and delivery. We describe the extensive experience with IMRT-based TBI at Stanford University and City of Hope Cancer Center. These groups, and others, have reported favorable clinical outcomes and have developed methods to optimize treatment planning and delivery. A critical next step is to evaluate the broader adoption of this approach. Therefore, IMRT-based TBI will be incorporated into a prospective, multi-institutional Children's Oncology Group study with careful procedures and safeguards in place.

Late effects following HSCT for childhood ALL: A national single-center study using three different modalities of delivery of total body irradiation.

BACKGROUND: Total body irradiation (TBI) is a pivotal part of conditioning prior to hematopoietic stem cell transplantation (HSCT) for childhood acute lymphoblastic leukemia (ALL), yet evidence is sparse regarding the effect of TBI delivery techniques on acute and late toxicities. DESIGN: In a national cohort of pediatric HSCT-recipients, we compared three TBI schedules; 12 Gray (Gy) delivered as (i) 4 Gy daily fractions from 2008 to 2011 (n = 12); (ii) 2 Gy fractions twice daily with two-dimensional (2D) planning technology from 2012 to 2015 (n = 16); and (iii) 2 Gy twice daily with three-dimensional (3D) planning intensity-modulated radiotherapy (IMRT) from 2016 to 2020 (n = 14). RESULTS: The 5-year event-free survival was 75.0%, 81.3%, and 81.3% in Cohorts 1, 2, and 3, respectively. Acute toxicity assessed as maximum ferritin and C-reactive protein during the first 3 months post HSCT did not differ between cohorts, nor did the time to first hospital discharge (median 28, 32, and 31 days, p = .25). The incidences of acute graft-versus-host disease (GvHD) (66%, 56%, 71%) and chronic GvHD (25%, 31%, 14%) were comparable. Pulmonary function assessed by spirometry did not differ significantly. The 5-year cataract-free survival was 33.3%, 79%, and 100% in Cohorts 1, 2, and 3, respectively. We found a nonsignificant tendency toward more endocrinopathies in Cohort 1 compared to Cohorts 2 and 3. CONCLUSION: The change of modality did not result in more relapses. More fractionation led to improvement with a lower incidence of cataract and a tendency toward fewer endocrinopathies. The effect of 3D-planning-IMRT technology requires further evaluation in larger studies.

Dose to organs at risk for total body irradiation: Single-institution data using the modulated arc total body irradiation technique.

BACKGROUND: Organs at risk (OAR) dose reporting for total body irradiation (TBI) patients is limited, and standardly reported only as mean doses to the lungs and kidneys. Consequently, dose received and effects on other OAR remain unexplored. To remedy this gap, this study reports dose data on an extensive list of OAR for patients treated at a single institution using the modulated arc total body irradiation (MATBI) technique. METHOD: An audit was undertaken of all patients treated with MATBI between January 2015 and March 2021 who had completed their course of treatment. OAR were contoured on MATBI patient treatment plans, with 12 Gy in six fraction prescription. OAR dose statistics and dose volume histogram data are reported for the whole body, lungs, kidneys, bones, brain, lens, heart, liver and bowel bag. RESULTS: The OAR dose data for 29 patients are reported. Mean dose results are body 11.77 Gy, lungs 9.86 Gy, kidneys 11.84 Gy, bones 12.03 Gy, brain 12.12 Gy, right lens 12.31 Gy, left lens 12.64 Gy, heart 11.07 Gy, liver 11.81 Gy and bowel bag 12.06 Gy. Dose statistics at 1-Gy intervals of V6-V13 for lungs and V10-V13 for kidneys are also included. CONCLUSION: This is the first time an extensive list of OAR data has been reported for any TBI technique. Due to the paucity of reporting, this information could be used by centres implementing the MATBI technique, in addition to aiding comparison between TBI techniques, with the potential for greater understanding of the relationship between dose volume data and toxicity.

Clinician's Ability to Identify Non-Melanoma Skin Cancer on 3D-Total Body Photography Sectors that Were Initially Identified during In-Person Skin Examination with Dermoscopy.

INTRODUCTION: Non-melanoma skin cancer (NMSC) is a cause of significant morbidity and mortality in high-risk individuals. Total body photography (TBP) is currently used to monitor melanocytic lesions in patients with high risk for melanoma. The authors examined if three-dimensional (3D)-TBP could be useful for diagnosis of NMSC. METHODS: Patients (n = 129; 52 female, 77 male) with lesions suspicious for NMSC who had not yet had a biopsy underwent clinical examination followed by examination of each lesion with 3D-TBP Vectra®WB360 (Canfield Scientific, Parsippany, NJ, USA) and dermoscopy. RESULTS: The 129 patients had a total of 182 lesions. Histological examination was performed for 158 lesions; the diagnoses included basal cell carcinoma (BCC; n = 107), squamous cell carcinoma (SCC; n = 27), in-situ SCC (n = 15). Lesions were located in the head/neck region (n = 138), trunk (n = 21), and limbs (n = 23). Of the 182 lesions examined, 12 were not visible on 3D-TBP; reasons for not being visible included location under hair and on septal of nose. Two lesions appeared only as erythema in 3D-TBP but were clearly identifiable on conventional photographs. Sensitivity of 3D-TBP was lower than that of dermoscopy for BCC (73% vs. 79%, p = 0.327), higher for SCC (81% vs. 74%, p = 0.727), and lower for in-situ SCC (0% vs. 33%, p = 125). Specificity of 3D-TBP was lower than that of dermoscopy for BCC (77% vs. 82%, 0.581), lower for SCC (75% vs. 84%, p = 0.063), and higher for in-situ SCC (97% vs. 94%, p = 0.344). Diagnostic accuracy of 3D-TBP was lower than that of dermoscopy for BCC (75% vs. 80%), lower for SCC (76% vs. 82%), and lower for in-situ SCC (88% vs. 89%). Lesion location was not associated with diagnostic confidence in dermoscopy (p = 0.152) or 3D-TBP (p = 0.353). If only lesions with high confidence were included in the calculation, diagnostic accuracy increased for BCC (n = 27; sensitivity 85%, specificity 85%, diagnostic accuracy 85%), SCC (n = 10; sensitivity 90%, specificity 80%, diagnostic accuracy 83%), and for in-situ SCC (n = 2; sensitivity 0%, specificity 100%, diagnostic accuracy 95%). CONCLUSION: Diagnostic accuracy appears to be slightly lower for 3D-TBP in comparison to dermoscopy. However, there is no statistically significant difference in the sensitivity and specificity of 3D-TBP and dermoscopy for NMSC. Diagnostic accuracy increases, if only lesions with high confidence are included in the calculation. Further studies are necessary to determine if 3D-TBP can improve management of NMSC.