We introduce the Fast Algorithm for Motion Correction (FALCON) software, which allows correction of both rigid and nonlinear motion artifacts in dynamic whole-body (WB) images, irrespective of the ...PET/CT system or the tracer.
Motion was corrected using affine alignment followed by a diffeomorphic approach to account for nonrigid deformations. In both steps, images were registered using multiscale image alignment. Moreover, the frames suited to successful motion correction were automatically estimated by calculating the initial normalized cross-correlation metric between the reference frame and the other moving frames. To evaluate motion correction performance, WB dynamic image sequences from 3 different PET/CT systems (Biograph mCT, Biograph Vision 600, and uEXPLORER) using 6 different tracers (
F-FDG,
F-fluciclovine,
Ga-PSMA,
Ga-DOTATATE,
C-Pittsburgh compound B, and
Rb) were considered. Motion correction accuracy was assessed using 4 different measures: change in volume mismatch between individual WB image volumes to assess gross body motion, change in displacement of a large organ (liver dome) within the torso due to respiration, change in intensity in small tumor nodules due to motion blur, and constancy of activity concentration levels.
Motion correction decreased gross body motion artifacts and reduced volume mismatch across dynamic frames by about 50%. Moreover, large-organ motion correction was assessed on the basis of correction of liver dome motion, which was removed entirely in about 70% of all cases. Motion correction also improved tumor intensity, resulting in an average increase in tumor SUVs by 15%. Large deformations seen in gated cardiac
Rb images were managed without leading to anomalous distortions or substantial intensity changes in the resulting images. Finally, the constancy of activity concentration levels was reasonably preserved (<2% change) in large organs before and after motion correction.
FALCON allows fast and accurate correction of rigid and nonrigid WB motion artifacts while being insensitive to scanner hardware or tracer distribution, making it applicable to a wide range of PET imaging scenarios.
We report Zika virus (ZIKV) vertical transmission in 130 infants born to PCR+ mothers at the time of the Rio de Janeiro epidemic of 2015-2016. Serum and urine collected from birth through the first ...year of life were tested by quantitative reverse transcriptase polymerase chain reaction (PCR) and/or IgM Zika MAC-ELISA. Four hundred and seven specimens are evaluated; 161 sera tested by PCR and IgM assays, 85 urines by PCR. Sixty-five percent of children (N = 84) are positive in at least one assay. Of 94 children tested within 3 months of age, 70% are positive. Positivity declines to 33% after 3 months. Five children are PCR+ beyond 200 days of life. Concordance between IgM and PCR results is 52%, sensitivity 65%, specificity 40% (positive PCR results as gold standard). IgM and serum PCR are 61% concordant; serum and urine PCR 55%. Most children (65%) are clinically normal. Equal numbers of children with abnormal findings (29 of 45, 64%) and normal findings (55 of 85, 65%) have positive results, p = 0.98. Earlier maternal trimester of infection is associated with positive results (p = 0.04) but not clinical disease (p = 0.98). ZIKV vertical transmission is frequent but laboratory confirmed infection is not necessarily associated with infant abnormalities.
Dual-ended readout depth-encoding detectors based on bismuth germanate (BGO) scintillation crystal arrays are good candidates for high-sensitivity small animal positron emission tomography used for ...very-low-dose imaging. In this paper, the performance of three dual-ended readout detectors based on 15 × 15 BGO arrays with three different reflector arrangements and 8 × 8 silicon photomultiplier arrays were evaluated and compared.
The three BGO arrays, denoted wo-ILG (without internal light guide), wp-ILG (with partial internal light guide), and wf-ILG (with full internal light guide), share a pitch size of 1.6 mm and thickness of 20 mm. Toray E60 with a thickness of 50
m was used as inter-crystal reflector. All reflector lengths in the wo-ILG and wf-ILG BGO arrays were 20 and 18 mm, respectively; the reflectors in the wp-ILG BGO array were 18 mm at the central region of the array and 20 mm at the edge. By using 18 mm reflectors, part of the crystals in the wp-ILG and wf-ILG BGO arrays worked as internal light guides.
The results showed that the detector based on the wo-ILG BGO array provided the best flood histogram. The energy, timing and DOI resolutions of the three detectors were similar. The energy resolutions full width at half maximum (FWHM value) based on the wo-ILG, wp-ILG and wf-ILG BGO arrays were 27.2 ± 3.9%, 28.7 ± 4.6%, and 29.5 ± 4.7%, respectively. The timing resolutions (FWHM value) were 4.7 ± 0.5 ns, 4.9 ± 0.5 ns, and 5.0 ± 0.6 ns, respectively. The DOI resolution (FWHM value) were 3.0 ± 0.2 mm, 2.9 ± 0.2 mm, and 3.0 ± 0.2 mm, respectively. Over all, the wo-ILG detector provided the best performance.
Members of the basic helix-loop-helix (bHLH) family of transcription factors have been shown to control critical aspects of development in many tissues. To identify bHLH genes that might regulate ...specific aspects of retinal cell development, we investigated the expression of bHLH genes in single, developing mouse retinal cells, with particular emphasis on the NeuroD family. Two of these factors, NeuroD2 and NeuroD6/NEX, had not been previously reported as expressed in the retina. A series of loss- and gain-of-function experiments was performed, which suggested that NeuroD genes have both similarities and differences in their activities. Notably, misexpression of NeuroD genes can direct amacrine cell processes to two to three specific sublaminae in the inner plexiform layer. This effect is specific to cell type and NeuroD gene, as the AII amacrine cell type is refractory to the effects of NeuroD1 and NeuroD6, but uniquely sensitive to the effect of NeuroD2 on neurite targeting. Additionally, NeuroD2 is endogenously expressed in AII amacrine cells, among others, and loss of NeuroD2 function results in a partial loss of AII amacrine cells. The effects of misexpressing NeuroD genes on retinal cell fate determination also suggested shared and divergent functions. Remarkably, NeuroD2 misexpression induced ganglion cell production even after the normal developmental window of ganglion cell genesis. Together, these data suggest that members of the NeuroD family are important for neuronal cell type identity and may be involved in several cell type-specific aspects of retinal development, including fate determination, differentiation, morphological development, and circuit formation.
Conventional whole-body static 18F-FDG PET imaging provides a semiquantitative evaluation of overall glucose metabolism without insight into the specific transport and metabolic steps. Here we ...demonstrate the ability of total-body multiparametric 18F-FDG PET to quantitatively evaluate glucose metabolism using macroparametric quantification and assess specific glucose delivery and phosphorylation processes using microparametric quantification for studying recovery from coronavirus disease 2019 (COVID-19). Methods: The study included 13 healthy subjects and 12 recovering COVID-19 subjects within 8 wk of confirmed diagnosis. Each subject had a 1-h dynamic 18F-FDG scan on the uEXPLORER total-body PET/CT system. Semiquantitative SUV and the SUV ratio relative to blood (SUVR) were calculated for different organs to measure glucose utilization. Tracer kinetic modeling was performed to quantify the microparametric blood-to-tissue 18F-FDG delivery rate K1 and the phosphorylation rate k3, as well as the macroparametric 18F-FDG net influx rate (K1). Statistical tests were performed to examine differences between healthy subjects and recovering COVID-19 subjects. The effect of COVID-19 vaccination was also investigated. Results: We detected no significant difference in lung SUV but significantly higher lung SUVR and K1 in COVID-19 recovery, indicating improved sensitivity of kinetic quantification for detecting the difference in glucose metabolism. A significant difference was also observed in the lungs with the phosphorylation rate k3 but not with K1, which suggests that glucose phosphorylation, rather than glucose delivery, drives the observed difference of glucose metabolism. Meanwhile, there was no or little difference in bone marrow 18F-FDG metabolism measured with SUV, SUVR, and K1 but a significantly higher bone marrow K1 in the COVID-19 group, suggesting a difference in glucose delivery. Vaccinated COVID-19 subjects had a lower lung K1 and a higher spleen K1 than unvaccinated COVID-19 subjects. Conclusion: Higher lung glucose metabolism and bone marrow glucose delivery were observed with total-body multiparametric 18F-FDG PET in recovering COVID-19 subjects than in healthy subjects, implying continued inflammation during recovery. Vaccination demonstrated potential protection effects. Total-body multiparametric PET of 18F-FDG can provide a more sensitive tool and more insights than conventional whole-body static 18F-FDG imaging to evaluate metabolic changes in systemic diseases such as COVID-19.
Quantitative kinetic modeling requires an input function. A noninvasive image-derived input function (IDIF) can be obtained from dynamic PET images. However, a robust IDIF location (e.g., aorta) may ...be far from a tissue of interest, particularly in total-body PET, introducing a time delay between the IDIF and the tissue. The standard practice of joint estimation (JE) of delay, along with model fitting, is computationally expensive. To improve the efficiency of delay correction for total-body PET parametric imaging, this study investigated the use of pulse timing methods to estimate and correct for delay.
Simulation studies were performed with a range of delay values, frame lengths, and noise levels to test the tolerance of 2 pulse timing methods-leading edge (LE) and constant fraction discrimination and their thresholds. The methods were then applied to data from 21 subjects (14 healthy volunteers, 7 cancer patients) who underwent a 60-min dynamic total-body
F-FDG PET acquisition. Region-of-interest kinetic analysis was performed and parametric images were generated to compare LE and JE methods of delay correction, as well as no delay correction.
Simulations demonstrated that a 10% LE threshold resulted in biases and SDs at tolerable levels for all noise levels tested, with 2-s frames. Pooled region-of-interest-based results (
= 154) showed strong agreement between LE (10% threshold) and JE methods in estimating delay (Pearson
0.96,
0.001) and the kinetic parameters
(
0.96,
0.001),
(
1.00,
0.001), and
(
0.97,
0.001). When tissues with minimal delay were excluded from pooled analyses, there were reductions in
(69.4%) and
(4.8%) when delay correction was not performed. Similar results were obtained for parametric images; additionally, lesion
contrast was improved overall with LE and JE delay correction compared with no delay correction and Patlak analysis.
This study demonstrated the importance of delay correction in total-body PET. LE delay correction can be an efficient surrogate for JE, requiring a fraction of the computational time and allowing for rapid delay correction across more than 10
voxels in total-body PET datasets.
This study aimed to comprehensively report complications associated with pelvic exenteration and to determine the strength of associations between three different grading methodologies and length of ...stay, quality-of-life as well as physical outcomes.
It is generally accepted that pelvic exenteration is associated with high rates of surgical morbidity. However, methods of reporting in the literature are inconsistent, making it difficult to compare surgical outcomes across studies to determine impact of surgery on patients.
This was a retrospective study.
This study was conducted at Royal Prince Alfred Hospital, Sydney. Australia.
It included patients who underwent pelvic exenteration between December 2016 and August 2019.
Complications were classified according to the Clavien-Dindo Classification, Comprehensive Complication Index and number of postoperative complications. Correlations between length of stay, physical component score, 6-minute walk test and sit-to-stand test; and complications as graded using Clavien-Dindo Classification, CCI and number of complications were explored using Pearson's or Point Biserial Correlation tests.
A total of 198 patients were included in this study. Clavien-Dindo Classification was moderately positively correlated with length of stay (r = 0.519, p < 0.0001), whereas Comprehensive Complication Index (r = 0.744, p < 0.0001) and the number of complications (r = 0.751, p < 0.0001) showed a strong correlation with length of stay. All these methodologies were moderately inversely correlated with predischarge 6-minute walk test (Clavien-Dindo Classification: r = -0.359, p = 0.008; Comprehensive Complication Index: r = -0.388, p = 0.007; number of complications: r = -0.467, p < 0.0001).
A single center retrospective study involves a small sample size. Classification of grade I and II complications in this cohort of patients who tend to have complex postoperative recovery was challenging and therefore incomplete. The incomplete data may have affected the correlations.
Comprehensive Complication Index and the number of postoperative complications were stronger correlated with length of stay than Clavien-Dindo Classification in pelvic exenteration patients. Comprehensive Complication Index may be a better grading system to classify postoperative complications following pelvic exenteration. See Video Abstract at http://links.lww.com/DCR/B906 .
Positron emission tomography (PET) using scanners incorporating lutetium-based (Lu-based) scintillators are widely used in nuclear medicine. However their application in imaging very low (<100 kBq) ...activity distributions is quite limited due to the intrinsic 176Lu radiation emitted from the scintillators. To visualize very low activities, 176Lu background needs to be reduced or removed. This study proposes a classification method to select background coincidences from true coincidences arising from the source by supervised learning using the optimal classifier as determined by investigating 5 different classifiers: logistic regression, support vector machine, random forest, extreme gradient boosting (XGBoost) and deep neural network. Five energy and time-of-flight (TOF) related features from each coincidence event are extracted to form the training and test set in the classification. The proposed method was verified on a pair of TOF-PET detector modules. Since the measured source coincidences cannot be differentiated from the background events experimentally, simulated source coincidences are used to train the classification model. The simulated feature spectra are therefore compared with those obtained from measurement to verify the feasibility of classifying measured coincidences using a model learned by simulation. XGBoost classifier performed most effectively in classifying the coincidences and provided impressively high classification accuracy (>99%). It was subsequently tested by imaging point-like source, planar Derenzo and bar phantoms with the pair of TOF-PET detectors. An 89.4% image contrast enhancement for the Derenzo phantom at an activity concentration of 100 Bq mm−2, and a 52.4% peak-to-valley ratio improvement across the area of bar phantom at a concentration of 25 Bq mm−2, were observed on the reconstructed images with XGBoost classification applied. The proposed method could extend the usage of Lu-based PET scanners to very low activity detection and imaging and has the potential to be used in a variety of molecular imaging tasks to detect low-level signals.
Purpose: Nonviolent communication (NVC) has been increasingly recognized as a potentially beneficial approach that could promote empathy, resolve conflicts, and improve psychosocial well-being. No ...validated measure is available to assess or quantify NVC-specific characteristics or behaviors. This paper describes the development and pilot psychometric evaluation of a self-report measure for assessing behaviors characteristic of NVC (e.g., awareness of feelings, honest self-expression). Method: We analyzed data in an online convenience sample of young adults (N = 205). Results: The 7-item Nonviolent Communication Behaviors Scale (NVCBS) was found to have satisfactory internal consistency (α = 0.789 to 0.810), good test-retest reliability (ICC = 0.781) and a single-factor structure. The NVCBS was also positively correlated with empathy while negatively correlated with negative beliefs about emotions, demonstrating its construct validity. Discussion: The study provides a reliable and valid measure of NVC behaviors which can facilitate future studies on NVC. Directions for future research are discussed.
Abstract
Friedreich’s ataxia (FRDA) is a severe multisystem disease caused by transcriptional repression induced by expanded GAA repeats located in intron 1 of the Frataxin (FXN) gene encoding ...frataxin. FRDA results from decreased levels of frataxin; thus, stabilization of the FXN mRNA already present in patient cells represents an attractive and unexplored therapeutic avenue. In this work, we pursued a novel approach based on oligonucleotide-mediated targeting of FXN mRNA ends to extend its half-life and availability as a template for translation. We demonstrated that oligonucleotides designed to bind to FXN 5′ or 3′ noncoding regions can increase FXN mRNA and protein levels. Simultaneous delivery of oligonucleotides targeting both ends increases efficacy of the treatment. The approach was confirmed in several FRDA fibroblast and induced pluripotent stem cell-derived neuronal progenitor lines. RNA sequencing and single-cell expression analyses confirmed oligonucleotide-mediated FXN mRNA upregulation. Mechanistically, a significant elongation of the FXN mRNA half-life without any changes in chromatin status at the FXN gene was observed upon treatment with end-targeting oligonucleotides, indicating that transcript stabilization is responsible for frataxin upregulation. These results identify a novel approach toward upregulation of steady-state mRNA levels via oligonucleotide-mediated end targeting that may be of significance to any condition resulting from transcription downregulation.
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