49 research outputs found
First-in-man evaluation of 124I-PGN650: A PET tracer for detecting phosphatidylserine as a biomarker of the solid tumor microenvironment
Purpose: PGN650 is a F(ab′) 2 antibody fragment that targets phosphatidylserine (PS), a marker normally absent that becomes exposed on tumor cells and tumor vasculature in response to oxidative stress and increases in response to therapy. PGN650 was labeled with 124 I to create a positron emission tomography (PET) agent as an in vivo biomarker for tumor microenvironment and response to therapy. In this phase 0 study, we evaluated the pharmacokinetics, safety, radiation dosimetry, and tumor targeting of this tracer in a cohort of patients with cancer. Methods: Eleven patients with known solid tumors received approximately 140 MBq (3.8 mCi) 124 I-PGN650 intravenously and underwent positron emission tomography–computed tomography (PET/CT) approximately 1 hour, 3 hours, and either 24 hours or 48 hours later to establish tracer kinetics for the purpose of calculating radiation dosimetry (from integration of the organ time-activity curves and OLINDA/EXM using the adult male and female models). Results: Known tumor foci demonstrated mildly increased uptake, with the highest activity at the latest imaging time. There were no unexpected adverse events. The liver was the organ receiving the highest radiation dose (0.77 mGy/MBq); the effective dose was 0.41 mSv/MBq. Conclusion: Although 124 I-PGN650 is safe for human PET imaging, the tumor targeting with this agent in patients was less than previously observed in animal studies
Fully automated 3D segmentation of dopamine transporter SPECT images using an estimation-based approach
Quantitative measures of uptake in caudate, putamen, and globus pallidus in
dopamine transporter (DaT) brain SPECT have potential as biomarkers for the
severity of Parkinson disease. Reliable quantification of uptake requires
accurate segmentation of these regions. However, segmentation is challenging in
DaT SPECT due to partial-volume effects, system noise, physiological
variability, and the small size of these regions. To address these challenges,
we propose an estimation-based approach to segmentation. This approach
estimates the posterior mean of the fractional volume occupied by caudate,
putamen, and globus pallidus within each voxel of a 3D SPECT image. The
estimate is obtained by minimizing a cost function based on the binary
cross-entropy loss between the true and estimated fractional volumes over a
population of SPECT images, where the distribution of the true fractional
volumes is obtained from magnetic resonance images from clinical populations.
The proposed method accounts for both the sources of partial-volume effects in
SPECT, namely the limited system resolution and tissue-fraction effects. The
method was implemented using an encoder-decoder network and evaluated using
realistic clinically guided SPECT simulation studies, where the ground-truth
fractional volumes were known. The method significantly outperformed all other
considered segmentation methods and yielded accurate segmentation with dice
similarity coefficients of ~ 0.80 for all regions. The method was relatively
insensitive to changes in voxel size. Further, the method was relatively robust
up to +/- 10 degrees of patient head tilt along transaxial, sagittal, and
coronal planes. Overall, the results demonstrate the efficacy of the proposed
method to yield accurate fully automated segmentation of caudate, putamen, and
globus pallidus in 3D DaT-SPECT images
DEMIST: A deep-learning-based task-specific denoising approach for myocardial perfusion SPECT
There is an important need for methods to process myocardial perfusion
imaging (MPI) SPECT images acquired at lower radiation dose and/or acquisition
time such that the processed images improve observer performance on the
clinical task of detecting perfusion defects. To address this need, we build
upon concepts from model-observer theory and our understanding of the human
visual system to propose a Detection task-specific deep-learning-based approach
for denoising MPI SPECT images (DEMIST). The approach, while performing
denoising, is designed to preserve features that influence observer performance
on detection tasks. We objectively evaluated DEMIST on the task of detecting
perfusion defects using a retrospective study with anonymized clinical data in
patients who underwent MPI studies across two scanners (N = 338). The
evaluation was performed at low-dose levels of 6.25%, 12.5% and 25% and using
an anthropomorphic channelized Hotelling observer. Performance was quantified
using area under the receiver operating characteristics curve (AUC). Images
denoised with DEMIST yielded significantly higher AUC compared to corresponding
low-dose images and images denoised with a commonly used task-agnostic DL-based
denoising method. Similar results were observed with stratified analysis based
on patient sex and defect type. Additionally, DEMIST improved visual fidelity
of the low-dose images as quantified using root mean squared error and
structural similarity index metric. A mathematical analysis revealed that
DEMIST preserved features that assist in detection tasks while improving the
noise properties, resulting in improved observer performance. The results
provide strong evidence for further clinical evaluation of DEMIST to denoise
low-count images in MPI SPECT
Measurement repeatability of 18 F-FDG PET/CT versus 18 F-FDG PET/MRI in solid tumors of the pelvis
Knowledge of the within-subject variability o
Bone Material Analogues for PET/MRI Phantoms
Purpose: To develop bone material analogues that can be used in construction
of phantoms for simultaneous PET/MRI systems.
Methods: Plaster was used as the basis for the bone material analogues tested
in this study. It was mixed with varying concentrations of an iodinated CT
contrast, a gadolinium-based MR contrast agent, and copper sulfate to modulate
the attenuation properties and MRI properties (T1 and T2*). Attenuation was
measured with CT and 68Ge transmission scans, and MRI properties were measured
with quantitative ultrashort echo time pulse sequences. A proof-of-concept
skull was created by plaster casting.
Results: Undoped plaster has a 511 keV attenuation coefficient (~0.14 cm-1)
similar to cortical bone (0.10-0.15 cm-1), but slightly longer T1 (~500 ms) and
T2* (~1.2 ms) MR parameters compared to bone (T1 ~ 300 ms, T2* ~ 0.4 ms).
Doping with the iodinated agent resulted in increased attenuation with minimal
perturbation to the MR parameters. Doping with a gadolinium chelate greatly
reduced T1 and T2*, resulting in extremely short T1 values when the target T2*
values were reached, while the attenuation coefficient was unchanged. Doping
with copper sulfate was more selective for T2* shortening and achieved
comparable T1 and T2* values to bone (after 1 week of drying), while the
attenuation coefficient was unchanged.
Conclusions: Plaster doped with copper sulfate is a promising bone material
analogue for a PET/MRI phantom, mimicking the MR properties (T1 and T2*) and
511 keV attenuation coefficient of human cortical bone
NEMA NU 4-2008 Comparison of preclinical PET imaging systems
The National Electrical Manufacturers Association (NEMA)
standard NU 4-2008 for performance measurements of smallanimal
tomographs was recently published. Before this standard,
there were no standard testing procedures for preclinical
PET systems, and manufacturers could not provide clear
specifications similar to those available for clinical systems
under NEMA NU 2-1994 and 2-2001. Consequently, performance
evaluation papers used methods that were modified ad
hoc from the clinical PET NEMA standard, thus making
comparisons between systems difficult. Methods: We acquired
NEMA NU 4-2008 performance data for a collection of commercial
animal PET systems manufactured since 2000: micro-
PET P4, microPET R4, microPET Focus 120, microPET Focus
220, Inveon, ClearPET, Mosaic HP, Argus (formerly eXplore
Vista), VrPET, LabPET 8, and LabPET 12. The data included
spatial resolution, counting-rate performance, scatter fraction,
sensitivity, and image quality and were acquired using settings
for routine PET. Results: The data showed a steady improvement
in system performance for newer systems as compared
with first-generation systems, with notable improvements in
spatial resolution and sensitivity. Conclusion: Variation in system
design makes direct comparisons between systems from
different vendors difficult. When considering the results from
NEMA testing, one must also consider the suitability of the
PET system for the specific imaging task at hand.This work was funded by the Natural Sciences and Engineering Research Council of Canada under Discovery Grant 341628-2007. No other potential conflict of interest relevant to this article was reported.En prens
The impact of surgical delay on resectability of colorectal cancer: An international prospective cohort study
AIM: The SARS-CoV-2 pandemic has provided a unique opportunity to explore the impact of surgical delays on cancer resectability. This study aimed to compare resectability for colorectal cancer patients undergoing delayed versus non-delayed surgery. METHODS: This was an international prospective cohort study of consecutive colorectal cancer patients with a decision for curative surgery (January-April 2020). Surgical delay was defined as an operation taking place more than 4 weeks after treatment decision, in a patient who did not receive neoadjuvant therapy. A subgroup analysis explored the effects of delay in elective patients only. The impact of longer delays was explored in a sensitivity analysis. The primary outcome was complete resection, defined as curative resection with an R0 margin. RESULTS: Overall, 5453 patients from 304 hospitals in 47 countries were included, of whom 6.6% (358/5453) did not receive their planned operation. Of the 4304 operated patients without neoadjuvant therapy, 40.5% (1744/4304) were delayed beyond 4 weeks. Delayed patients were more likely to be older, men, more comorbid, have higher body mass index and have rectal cancer and early stage disease. Delayed patients had higher unadjusted rates of complete resection (93.7% vs. 91.9%, P = 0.032) and lower rates of emergency surgery (4.5% vs. 22.5%, P < 0.001). After adjustment, delay was not associated with a lower rate of complete resection (OR 1.18, 95% CI 0.90-1.55, P = 0.224), which was consistent in elective patients only (OR 0.94, 95% CI 0.69-1.27, P = 0.672). Longer delays were not associated with poorer outcomes. CONCLUSION: One in 15 colorectal cancer patients did not receive their planned operation during the first wave of COVID-19. Surgical delay did not appear to compromise resectability, raising the hypothesis that any reduction in long-term survival attributable to delays is likely to be due to micro-metastatic disease
A scatter and randoms weighted (SRW) iterative PET reconstruction
Purpose: In positron emission tomography (PET) imaging, the main function of scatter and randoms corrections is to improve contrast and quantitative accuracy. Both corrections are essential and critically important. Several iterative reconstruction schemes incorporating scatter and randoms corrections have been developed over the years. In this work, the authors propose a new method to incorporate the scatter and randoms corrections into the iterative image reconstruction, which has shown promising results in regards to improving reconstruction performance and image quality as compared to the standard methods
Evaluation of attenuation correction in PET/MRI with synthetic lesion insertion
Purpose: One major challenge facing simultaneous positron emission tomography (PET)/ magnetic resonance imaging (MRI) is PET attenuation correction (AC) measurement and evaluation of its accuracy. There is a crucial need for the evaluation of current and emergent PET AC methodologies in terms of absolute quantitative accuracy in the reconstructed PET images. Approach: To address this need, we developed and evaluated a lesion insertion tool for PET/MRI that will facilitate this evaluation process. This tool was developed for the Biograph mMR and evaluated using phantom and patient data. Contrast recovery coefficients (CRC) from the NEMA IEC phantom of synthesized lesions were compared to measurements. In addition, SUV biases of lesions inserted in human brain and pelvis images were assessed from PET images reconstructed with MRI-based AC (MRAC) and CT-based AC (CTAC). Results: For cross-comparison PET/MRI scanners AC evaluation, we demonstrated that the developed lesion insertion tool can be harmonized with the GE-SIGNA lesion insertion tool. About <3% CRC curves difference between simulation and measurement was achieved. An average of 1.6% between harmonized simulated CRC curves obtained with mMR and SIGNA lesion insertion tools was achieved. A range of -5% to 12% MRAC to CTAC SUV bias was respectively achieved in the vicinity and inside bone tissues in patient images in two anatomical regions, the brain, and pelvis. Conclusions: A lesion insertion tool was developed for the Biograph mMR PET/MRI scanner and harmonized with the SIGNA PET/MRI lesion insertion tool. These tools will allow for an accurate evaluation of different PET/MRI AC approaches and permit exploration of subtle attenuation correction differences across systems
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Synthetic PET via Domain Translation of 3-D MRI
Historically, patient datasets have been used to develop and validate various reconstruction algorithms for PET/MRI and PET/CT. To enable such algorithm development, without the need for acquiring hundreds of patient exams, in this article we demonstrate a deep learning technique to generate synthetic but realistic whole-body PET sinograms from abundantly available whole-body MRI. Specifically, we use a dataset of 56 18F-FDG-PET/MRI exams to train a 3-D residual UNet to predict physiologic PET uptake from whole-body T1-weighted MRI. In training, we implemented a balanced loss function to generate realistic uptake across a large dynamic range and computed losses along tomographic lines of response to mimic the PET acquisition. The predicted PET images are forward projected to produce synthetic PET (sPET) time-of-flight (ToF) sinograms that can be used with vendor-provided PET reconstruction algorithms, including using CT-based attenuation correction (CTAC) and MR-based attenuation correction (MRAC). The resulting synthetic data recapitulates physiologic 18F-FDG uptake, e.g., high uptake localized to the brain and bladder, as well as uptake in liver, kidneys, heart, and muscle. To simulate abnormalities with high uptake, we also insert synthetic lesions. We demonstrate that this sPET data can be used interchangeably with real PET data for the PET quantification task of comparing CTAC and MRAC methods, achieving ≤ 7.6% error in mean-SUV compared to using real data. These results together show that the proposed sPET data pipeline can be reasonably used for development, evaluation, and validation of PET/MRI reconstruction methods