14 results on '"Lafontaine, D."'
Search Results
2. Fluorescent riboswitch-controlled biosensors for the genome scale analysis of metabolic pathways.
- Author
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Michaud, A., Garneau, D., Côté, J.-P., and Lafontaine, D. A.
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THIAMIN pyrophosphate ,RIBOSWITCHES ,BIOSENSORS ,REPORTER genes ,GREEN fluorescent protein ,GENOMES - Abstract
Fluorescent detection in cells has been tremendously developed over the years and now benefits from a large array of reporters that can provide sensitive and specific detection in real time. However, the intracellular monitoring of metabolite levels still poses great challenges due to the often complex nature of detected metabolites. Here, we provide a systematic analysis of thiamin pyrophosphate (TPP) metabolism in Escherichia coli by using a TPP-sensing riboswitch that controls the expression of the fluorescent gfp reporter. By comparing different combinations of reporter fusions and TPP-sensing riboswitches, we determine key elements that are associated with strong TPP-dependent sensing. Furthermore, by using the Keio collection as a proxy for growth conditions differing in TPP levels, we perform a high-throughput screen analysis using high-density solid agar plates. Our study reveals several genes whose deletion leads to increased or decreased TPP levels. The approach developed here could be applicable to other riboswitches and reporter genes, thus representing a framework onto which further development could lead to highly sophisticated detection platforms allowing metabolic screens and identification of orphan riboswitches. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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3. Decompositions of High-Frequency Helmholtz Solutions via Functional Calculus, and Application to the Finite Element Method
- Author
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Galkowski, J., primary, Lafontaine, D., additional, Spence, E. A., additional, and Wunsch, J., additional
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- 2023
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4. Abstract No. 155 Immediate 3D Imaging Assessment is the Most Accurate Predictor of Local Tumor Progression after Microwave Ablation of Colorectal Cancer Liver Metastases
- Author
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Zadeh, M. Zirakchian, primary, Kirov, A., additional, Lafontaine, D., additional, Yeh, R., additional, Kunin, H., additional, Solomon, S., additional, Erinjeri, J., additional, Sotirchos, V., additional, and Sofocleous, C., additional
- Published
- 2023
- Full Text
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5. Wavenumber-explicit convergence of the hp-FEM for the full-space heterogeneous Helmholtz equation with smooth coefficients
- Author
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Lafontaine, D., primary, Spence, E.A., additional, and Wunsch, J., additional
- Published
- 2022
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6. A sharp relative-error bound for the Helmholtz h-FEM at high frequency
- Author
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Lafontaine, D., primary, Spence, E. A., additional, and Wunsch, J., additional
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- 2021
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7. Mapping and engineering RNA-controlled architecture of the multiphase nucleolus.
- Author
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Quinodoz SA, Jiang L, Abu-Alfa AA, Comi TJ, Zhao H, Yu Q, Wiesner LW, Botello JF, Donlic A, Soehalim E, Zorbas C, Wacheul L, Košmrlj A, Lafontaine D, Klinge S, and Brangwynne CP
- Abstract
Biomolecular condensates are key features of intracellular compartmentalization. As the most prominent nuclear condensate in eukaryotes, the nucleolus is a layered multiphase liquid-like structure and the site of ribosome biogenesis. In the nucleolus, ribosomal RNAs (rRNAs) are transcribed and processed, undergoing multiple maturation steps that ultimately result in formation of the ribosomal small subunit (SSU) and large subunit (LSU). However, how rRNA processing is coupled to the layered nucleolar organization is poorly understood due to a lack of tools to precisely monitor and perturb nucleolar rRNA processing dynamics. Here, we developed two complementary approaches to spatiotemporally map rRNA processing and engineer de novo nucleoli. Using sequencing in parallel with imaging, we found that rRNA processing steps are spatially segregated, with sequential maturation of rRNA required for its outward movement through nucleolar phases. Furthermore, by generating synthetic de novo nucleoli through an engineered rDNA plasmid system in cells, we show that defects in SSU processing can alter the ordering of nucleolar phases, resulting in inside-out nucleoli and preventing rRNA outflux, while LSU precursors are necessary to build the outermost layer of the nucleolus. These findings demonstrate how rRNA is both a scaffold and substrate for the nucleolus, with rRNA acting as a programmable blueprint for the multiphase architecture that facilitates assembly of an essential molecular machine., Competing Interests: Competing interests C.P.B. is a scientific founder, Scientific Advisory Board member, shareholder, and consultant for Nereid Therapeutics.
- Published
- 2024
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8. Conventional and novel [ 18 F]FDG PET/CT features as predictors of CAR-T cell therapy outcome in large B-cell lymphoma.
- Author
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Leithner D, Flynn JR, Devlin SM, Mauguen A, Fei T, Zeng S, Zheng J, Imber BS, Hubbeling H, Mayerhoefer ME, Bedmutha A, Luttwak E, Corona M, Dahi PB, Luna de Abia A, Landego I, Lin RJ, Palomba ML, Scordo M, Park JH, Tomas AA, Salles G, Lafontaine D, Michaud L, Shah GL, Perales MA, Shouval R, and Schöder H
- Subjects
- Humans, Male, Female, Aged, Middle Aged, Adult, Treatment Outcome, Aged, 80 and over, Radiopharmaceuticals, Prognosis, Retrospective Studies, Fluorodeoxyglucose F18, Positron Emission Tomography Computed Tomography methods, Immunotherapy, Adoptive methods, Lymphoma, Large B-Cell, Diffuse therapy, Lymphoma, Large B-Cell, Diffuse diagnostic imaging
- Abstract
Relapse and toxicity limit the effectiveness of chimeric antigen receptor T-cell (CAR-T) therapy for large B-cell lymphoma (LBCL), yet biomarkers that predict outcomes and toxicity are lacking. We examined radiomic features extracted from pre-CAR-T
18 F-fluorodeoxyglucose positron emission tomography/computed tomography ([18 F]FDG PET/CT) scans (n = 341) of 180 patients (121 male; median age, 66 years). Three conventional (maximum standardized uptake value [SUVmax], metabolic tumor volume [MTV], total lesion glycolysis [TLG]) and 116 novel radiomic features were assessed, along with inflammatory markers, toxicities, and outcomes. At both pre-apheresis and pre-infusion time points, conventional PET features of disease correlated with elevated inflammatory markers. At pre-infusion, MTV was associated with grade ≥ 2 cytokine release syndrome (odds ratio [OR] for 100 mL increase: 1.08 [95% confidence interval (CI), 1.01-1.20], P = 0.031), and SUVmax was associated with failure to achieve complete response (CR) (OR 1.72 [95% CI, 1.24-2.43], P < 0.001). Higher pre-apheresis and pre-infusion MTV values were associated with shorter progression-free survival (PFS) (HR for 10-unit increase: 1.11 [95% CI, 1.05-1.17], P < 0.001; 1.04 [95% CI, 1.02-1.07], P < 0.001) and shorter overall survival (HR for 100-unit increase: 1.14 [95% CI, 1.07-1.21], P < 0.001; 1.04 [95% CI, 1.02-1.06], P < 0.001). A combined MTV and LDH measure stratified patients into high and low PFS risk groups. Multiple pre-infusion novel radiomic features were associated with CR. These quantitative conventional [18 F]FDG PET/CT features obtained before CAR-T cell infusion, which were correlated with inflammation markers, may provide prognostic biomarkers for CAR-T therapy efficacy and toxicity. The use of conventional and novel radiomic features may thus help identify high-risk patients for earlier interventions., (© 2024. The Author(s).)- Published
- 2024
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9. Three-Dimensional Margin as a Predictor of Local Tumor Progression after Microwave Ablation: Intraprocedural versus 4-8-Week Postablation Assessment.
- Author
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Zirakchian Zadeh M, Sotirchos VS, Kirov A, Lafontaine D, Gönen M, Yeh R, Kunin H, Petre EN, Kitsel Y, Elsayed M, Solomon SB, Erinjeri JP, Schwartz LH, and Sofocleous CT
- Subjects
- Humans, Treatment Outcome, Prospective Studies, Microwaves adverse effects, Retrospective Studies, Catheter Ablation adverse effects, Catheter Ablation methods, Liver Neoplasms diagnostic imaging, Liver Neoplasms surgery, Liver Neoplasms secondary
- Abstract
Purpose: To evaluate the prognostic accuracy of intraprocedural and 4-8-week (current standard) post-microwave ablation zone (AZ) and margin assessments for prediction of local tumor progression (LTP) using 3-dimensional (3D) software., Materials and Methods: Data regarding 100 colorectal liver metastases (CLMs) in 75 patients were collected from 2 prospective fluorodeoxyglucose positron emission tomography (PET)/computed tomography (CT)-guided microwave ablation (MWA) trials. The target CLMs and theoretical 5- and 10-mm margins were segmented and registered intraprocedurally and at 4-8 weeks after MWA contrast-enhanced CT (or magnetic resonance [MR] imaging) using the same methodology and 3D software. Tumor and 5- and 10-mm minimal margin (MM) volumes not covered by the AZ were defined as volumes of insufficient coverage (VICs). The intraprocedural and 4-8-week post-MWA VICs were compared as predictors of LTP using receiver operating characteristic curve analysis., Results: The median follow-up time was 19.6 months (interquartile range, 7.97-36.5 months). VICs for 5- and 10-mm MMs were predictive of LTP at both time assessments. The highest accuracy for the prediction of LTP was documented with the intra-ablation 5-mm VIC (area under the curve [AUC], 0.78; 95% confidence interval, 0.66-0.89). LTP for a VIC of 6-10-mm margin category was 11.4% compared with 4.3% for >10-mm margin category (P < .001)., Conclusions: A 3D 5-mm MM is a critical endpoint of thermal ablation, whereas optimal local tumor control is noted with a 10-mm MM. Higher AUCs for prediction of LTP were achieved for intraprocedural evaluation than for the 4-8-week postablation 3D evaluation of the AZ., (Copyright © 2024 SIR. Published by Elsevier Inc. All rights reserved.)
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- 2024
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10. Lesion Dosimetry for [ 177 Lu]Lu-PSMA-617 Radiopharmaceutical Therapy Combined with Stereotactic Body Radiotherapy in Patients with Oligometastatic Castration-Sensitive Prostate Cancer.
- Author
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Grkovski M, O'Donoghue JA, Imber BS, Andl G, Tu C, Lafontaine D, Schwartz J, Thor M, Zelefsky MJ, Humm JL, and Bodei L
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- Male, Humans, Radiopharmaceuticals adverse effects, Positron Emission Tomography Computed Tomography, Prospective Studies, Dipeptides therapeutic use, Prostate-Specific Antigen, Heterocyclic Compounds, 1-Ring therapeutic use, Castration, Lutetium therapeutic use, Radiosurgery, Prostatic Neoplasms, Castration-Resistant pathology
- Abstract
A single-institution prospective pilot clinical trial was performed to demonstrate the feasibility of combining [
177 Lu]Lu-PSMA-617 radiopharmaceutical therapy (RPT) with stereotactic body radiotherapy (SBRT) for the treatment of oligometastatic castration-sensitive prostate cancer. Methods: Six patients with 9 prostate-specific membrane antigen (PSMA)-positive oligometastases received 2 cycles of [177 Lu]Lu-PSMA-617 RPT followed by SBRT. After the first intravenous infusion of [177 Lu]Lu-PSMA-617 (7.46 ± 0.15 GBq), patients underwent SPECT/CT at 3.2 ± 0.5, 23.9 ± 0.4, and 87.4 ± 12.0 h. Voxel-based dosimetry was performed with calibration factors (11.7 counts per second/MBq) and recovery coefficients derived from in-house phantom experiments. Lesions were segmented on baseline PSMA PET/CT (50% SUVmax ). After a second cycle of [177 Lu]Lu-PSMA-617 (44 ± 3 d; 7.50 ± 0.10 GBq) and an interim PSMA PET/CT scan, SBRT (27 Gy in 3 fractions) was delivered to all PSMA-avid oligometastatic sites, followed by post-PSMA PET/CT. RPT and SBRT voxelwise dose maps were scaled (α/β = 3 Gy; repair half-time, 1.5 h) to calculate the biologically effective dose (BED). Results: All patients completed the combination therapy without complications. No grade 3+ toxicities were noted. The median of the lesion SUVmax as measured on PSMA PET was 16.8 (interquartile range [IQR], 11.6) (baseline), 6.2 (IQR, 2.7) (interim), and 2.9 (IQR, 1.4) (post). PET-derived lesion volumes were 0.4-1.7 cm3 The median lesion-absorbed dose (AD) from the first cycle of [177 Lu]Lu-PSMA-617 RPT (ADRPT ) was 27.7 Gy (range, 8.3-58.2 Gy; corresponding to 3.7 Gy/GBq, range, 1.1-7.7 Gy/GBq), whereas the median lesion AD from SBRT was 28.1 Gy (range, 26.7-28.8 Gy). Spearman rank correlation, ρ, was 0.90 between the baseline lesion PET SUVmax and SPECT SUVmax ( P = 0.005), 0.74 ( P = 0.046) between the baseline PET SUVmax and the lesion ADRPT , and -0.81 ( P = 0.022) between the lesion ADRPT and the percent change in PET SUVmax (baseline to interim). The median for the lesion BED from RPT and SBRT was 159 Gy (range, 124-219 Gy). ρ between the BED from RPT and SBRT and the percent change in PET SUVmax (baseline to post) was -0.88 ( P = 0.007). Two cycles of [177 Lu]Lu-PSMA-617 RPT contributed approximately 40% to the maximum BED from RPT and SBRT. Conclusion: Lesional dosimetry in patients with oligometastatic castration-sensitive prostate cancer undergoing [177 Lu]Lu-PSMA-617 RPT followed by SBRT is feasible. Combined RPT and SBRT may provide an efficient method to maximize the delivery of meaningful doses to oligometastatic disease while addressing potential microscopic disease reservoirs and limiting the dose exposure to normal tissues., (© 2023 by the Society of Nuclear Medicine and Molecular Imaging.)- Published
- 2023
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11. MIRD Pamphlet No. 28, Part 2: Comparative Evaluation of MIRDcalc Dosimetry Software Across a Compendium of Diagnostic Radiopharmaceuticals.
- Author
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Carter LM, Ocampo Ramos JC, Olguin EA, Brown JL, Lafontaine D, Jokisch DW, Bolch WE, and Kesner AL
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- Humans, Radiometry, Software, Phantoms, Imaging, Radiation Dosage, Radiopharmaceuticals, Pamphlets
- Abstract
Radiopharmaceutical dosimetry is usually estimated via organ-level MIRD schema-style formalisms, which form the computational basis for commonly used clinical and research dosimetry software. Recently, MIRDcalc internal dosimetry software was developed to provide a freely available organ-level dosimetry solution that incorporates up-to-date models of human anatomy, addresses uncertainty in radiopharmaceutical biokinetics and patient organ masses, and offers a 1-screen user interface as well as quality assurance tools. The present work describes the validation of MIRDcalc and, secondarily, provides a compendium of radiopharmaceutical dose coefficients obtained with MIRDcalc. Biokinetic data for about 70 currently and historically used radiopharmaceuticals were obtained from the International Commission on Radiological Protection (ICRP) publication 128 radiopharmaceutical data compendium. Absorbed dose and effective dose coefficients were derived from the biokinetic datasets using MIRDcalc, IDAC-Dose, and OLINDA software. The dose coefficients obtained with MIRDcalc were systematically compared against the other software-derived dose coefficients and those originally presented in ICRP publication 128. Dose coefficients computed with MIRDcalc and IDAC-Dose showed excellent overall agreement. The dose coefficients derived from other software and the dose coefficients promulgated in ICRP publication 128 both were in reasonable agreement with the dose coefficients computed with MIRDcalc. Future work should expand the scope of the validation to include personalized dosimetry calculations., (© 2023 by the Society of Nuclear Medicine and Molecular Imaging.)
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- 2023
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12. MIRD Pamphlet No. 28, Part 1: MIRDcalc-A Software Tool for Medical Internal Radiation Dosimetry.
- Author
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Kesner AL, Carter LM, Ramos JCO, Lafontaine D, Olguin EA, Brown JL, President B, Jokisch DW, Fisher DR, and Bolch WE
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- Humans, Software, Radioisotopes, Radiotherapy Dosage, Pamphlets, Radiometry methods
- Abstract
Medical internal radiation dosimetry constitutes a fundamental aspect of diagnosis, treatment, optimization, and safety in nuclear medicine. The MIRD committee of the Society of Nuclear Medicine and Medical Imaging developed a new computational tool to support organ-level and suborgan tissue dosimetry (MIRDcalc, version 1). Based on a standard Excel spreadsheet platform, MIRDcalc provides enhanced capabilities to facilitate radiopharmaceutical internal dosimetry. This new computational tool implements the well-established MIRD schema for internal dosimetry. The spreadsheet incorporates a significantly enhanced database comprising details for 333 radionuclides, 12 phantom reference models (International Commission on Radiological Protection), 81 source regions, and 48 target regions, along with the ability to interpolate between models for patient-specific dosimetry. The software also includes sphere models of various composition for tumor dosimetry. MIRDcalc offers several noteworthy features for organ-level dosimetry, including modeling of blood source regions and dynamic source regions defined by user input, integration of tumor tissues, error propagation, quality control checks, batch processing, and report-preparation capabilities. MIRDcalc implements an immediate, easy-to-use single-screen interface. The MIRDcalc software is available for free download (www.mirdsoft.org) and has been approved by the Society of Nuclear Medicine and Molecular Imaging., (© 2023 by the Society of Nuclear Medicine and Molecular Imaging.)
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- 2023
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13. TriDFusion (3DF) image viewer.
- Author
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Lafontaine D, Schmidtlein CR, Kirov A, Reddy RP, Krebs S, Schöder H, and Humm JL
- Abstract
Background: An open-source, extensible medical viewing platform is described, called the TriDFusion image viewer (3DF). The 3DF addresses many broad unmet needs in nuclear medicine research; it provides a viewer with several tools not available in commercial nuclear medicine workstations, yet invaluable for imaging in research studies., Results: The 3DF includes an image integration platform to register images from multiple imaging modalities together with delineated volumes of interest (VOIs), structures and dose distributions. It can process images from different vendors' systems and is therefore vendor neutral. The 3DF also provides a convenient tool for performing multi-modality image analysis and fusion. The functional components currently being distributed is open-source code that includes: (1) a high quality viewer that can display axial, coronal, and sagittal tomographic images, maximum intensity projection images, structure contours, and isointensity contour lines or dose colorwash, (2) multi-image fusion allowing multiple images to be fused with VOI and dose distributions, (3) a suite of segmentation tools to edit and/or create tumor and organ VOIs, (4) dosimetry tools for several radioisotopes, (5) clinical tools for correcting acquisition errors, including patient orientation, and (6) the ability to save the resultant image and VOI as DICOM files or to export the numerical results as comma separated values files. Because the code is written in MATLAB™, it is highly readable and is easier for the coder to make changes compared to languages such as C or C++. In what follows, we describe the content of the new TriDFusion (3DF) image viewer software platform using examples of a number of clinical research workflows. Such examples vary in complexity but illustrate the main attributes of the software., Conclusions: In summary, 3DF provides a powerful, convenient, easy-to-use suite of open-source imaging research tools for the nuclear medicine community that allows physicians, medical physicists, and academic researchers to display, manipulate, and analyze images., (© 2022. The Author(s).)
- Published
- 2022
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14. The Quest for an Accurate Functional Tumor Volume with 68 Ga-DOTATATE PET/CT.
- Author
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Reddy RP, Ross Schmidtlein C, Giancipoli RG, Mauguen A, LaFontaine D, Schoder H, and Bodei L
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- Gallium Radioisotopes, Humans, Positron Emission Tomography Computed Tomography, Positron-Emission Tomography, Radionuclide Imaging, Radiopharmaceuticals, Somatostatin, Tumor Burden, Neuroendocrine Tumors metabolism, Organometallic Compounds metabolism
- Abstract
68 Ga-labeled somatostatin analog (SSA) PET/CT is now a standard-of-care component in the management of neuroendocrine tumors (NETs). However, treatment response for NETs is still assessed with morphologic size measurements from other modalities, which can result in inaccuracy about the disease burden. Functional tumor volume (FTV) acquired from SSA PET/CT has been suggested as a possible metric, but no validated measurement tool to measure FTV exists. We tested the precision of multiple FTV computational approaches compared with morphologic volume measurements to identify a candidate for incorporation into future FTV studies to assess tumor burden more completely and accurately. Methods: The clinical and imaging data of 327 NET patients were collected at Memorial Sloan Kettering Cancer Center between December 2016 and April 2018. Patients were required to have SSA PET/CT and dedicated CT scans within 6 wk and were excluded if they had any intervention between scans. When paired studies were evaluated, 150 correlating lesions demonstrated SSA. Lesions were excluded if they contained necrotic components or were lobulated. This exclusion resulted in 94 lesions in 20 patients. The FTV for each lesion was evaluated with a hand-drawn assessment and 3 automated techniques: 50% threshold from SUVmax , 42% threshold from SUVmax , and background-subtracted lesion activity. These measurements were compared with volume calculated from morphologic volume measurements. Results: The FTV calculation methods showed varying correlations with morphologic volume measurements. FTV using a 42% threshold had a 0.706 correlation, hand-drawn volume from PET imaging had a 0.657 correlation, FTV using a 50% threshold had a 0.645 correlation, and background-subtracted lesion activity had a 0.596 correlation. The Bland-Altman plots indicated that all FTV methods had a positive mean difference from morphologic volume, with a 50% threshold showing the smallest mean difference. Conclusion: FTV determined with thresholding of SUVmax demonstrated the strongest correlation with traditional morphologic lesion volume assessment and the least bias. This method was more accurate than FTV calculated from hand-drawn volume assessments. Threshold-based automated FTV assessment promises to better determine disease extent and prognosis in patients with NETs., (© 2022 by the Society of Nuclear Medicine and Molecular Imaging.)- Published
- 2022
- Full Text
- View/download PDF
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