scholarly journals Bias evaluation and reduction in 3D OP-OSEM reconstruction in dynamic equilibrium PET studies with 11C-labeled for binding potential analysis

PLoS ONE ◽  
2021 ◽  
Vol 16 (1) ◽  
pp. e0245580
Author(s):  
Cláudia Régio Brambilla ◽  
Jürgen Scheins ◽  
Ahlam Issa ◽  
Lutz Tellmann ◽  
Hans Herzog ◽  
...  
Keyword(s):  
Dynamic Equilibrium ◽  
Binding Potential ◽  
Time Range ◽  
Acquisition Time ◽  
Time Interval ◽  
Task Effects ◽  
Positron Emission ◽  
Linear Slope ◽  
The Impact ◽  
Bias Evaluation

Iterative image reconstruction is widely used in positron emission tomography. However, it is known to contribute to quantitation bias and is particularly pronounced during dynamic studies with 11C-labeled radiotracers where count rates become low towards the end of the acquisition. As the strength of the quantitation bias depends on the counts in the reconstructed frame, it can differ from frame to frame of the acquisition. This is especially relevant in the case of neuro-receptor studies with simultaneous PET/MR when a bolus-infusion protocol is applied to allow the comparison of pre- and post-task effects. Here, count dependent changes in quantitation bias may interfere with task changes. We evaluated the impact of different framing schemes on quantitation bias and its propagation into binding potential (BP) using a phantom decay study with 11C and 3D OP-OSEM. Further, we propose a framing scheme that keeps the true counts per frame constant over the acquisition time as constant framing schemes and conventional increasing framing schemes are unlikely to achieve stable bias values during the acquisition time range. For a constant framing scheme with 5 minutes frames, the BP bias was 7.13±2.01% (10.8% to 3.8%) compared to 5.63±2.85% (7.8% to 4.0%) for conventional increasing framing schemes. Using the proposed constant true counts framing scheme, a stabilization of the BP bias was achieved at 2.56±3.92% (3.5% to 1.7%). The change in BP bias was further studied by evaluating the linear slope during the acquisition time interval. The lowest slope values were observed in the constant true counts framing scheme. The constant true counts framing scheme was effective for BP bias stabilization at relevant activity and time ranges. The mean BP bias under these conditions was 2.56±3.92%, which represents the lower limit for the detection of changes in BP during equilibrium and is especially important in the case of cognitive tasks where the expected changes are low.

scholarly journals Bias Evaluation and Reduction in 3D OP-OSEM Reconstruction in Dynamic Equilibrium PET Studies

2020 ◽  
Author(s):  
Cláudia Régio Brambilla ◽  
Jürgen Scheins ◽  
Ahlam Issa ◽  
Lutz Tellmann ◽  
Hans Herzog ◽  
...  
Keyword(s):  
Image Reconstruction ◽  
Activity Concentration ◽  
Binding Potential ◽  
Acquisition Time ◽  
Time Interval ◽  
Reconstruction Method ◽  
Reconstruction Algorithms ◽  
Binding Studies ◽  
Data Set ◽  
The Impact

Abstract Background: Iterative image reconstruction algorithms are widely used in positron emission tomography (PET). However, they are known to contribute to quantitation bias, which is particularly pronounced during dynamic PET studies such as neuroreceptor binding studies with 11C-labelled radiotracers where count rates become low towards the end of the examination. This problem is relevant in case simultaneous PET/MR studies which apply a bolus-infusion protocol to allow the multimodal comparison between control or resting state and stimulation effects in a single session of e.g. 60 min, i.e. 3 half-lives of 11C. A quantitation bias may interfere with stimulation related changes. In this study, we evaluated the impact of the 3D ordinary Poisson OSEM (3D OP-OSEM) on quantitation accuracy reconstructions and the subsequent propagation into binding potential values using a decay study of a 11C filled phantom and a human brain data set. To evaluate the reconstruction bias, we tested different reconstruction framing schemes and propose a framing scheme that keeps the counts per time frame constant over the full acquisition time. We also compared the vendor’s 3D OP-OSEM image reconstruction method to an in-house developed reconstruction (PRESTO toolkit). Results: In general, a bias for low and high activity concentration regions was observed in the range of ± 3% and - 3% to 5%, respectively. Using the alternative proposed framing scheme, a lower bias was achieved for regions with low activity concentration using PRESTO, and a stabilization of the mean bias for the binding potential was achieved at around 5% with the vendor’s reconstruction throughout the relevant activity curve time interval. Conclusions: The bias in activity concentration propagated into the binding potential values leading to a mean bias of around 5%, thus allowing the detection of changes in binding values during equilibrium of > 5%.

scholarly journals Pancreatic GLP-1r binding potential is reduced in insulin-resistant pigs

2020 ◽  
Vol 8 (2) ◽  
pp. e001540
Author(s):  
Charles-Henri Malbert ◽  
Alain Chauvin ◽  
Michael Horowitz ◽  
Karen L Jones
Keyword(s):  
Type 2 Diabetes ◽  
Tissue Perfusion ◽  
Binding Potential ◽  
Insulin Resistant ◽  
Positron Emission ◽  
Glucagon Like Peptide 1 ◽  
Design And Methods ◽  
Insulinotropic Effect ◽  
The Impact

IntroductionThe insulinotropic capacity of exogenous glucagon like peptide-1 (GLP-1) is reduced in type 2 diabetes and the insulin-resistant obese. We have tested the hypothesis that this response is the consequence of a reduced pancreatic GLP-1 receptor (GLP-1r) density in insulin-resistant obese animals.Research design and methodsGLP-1r density was measured in lean and insulin-resistant adult miniature pigs after the administration of a 68Ga-labeled GLP-1r agonist. The effect of hyperinsulinemia on GLP-1r was assessed using sequential positron emission tomography (PET), both in the fasted state and during a clamp. The impact of tissue perfusion, which could account for changes in GLP-1r agonist uptake, was also investigated using 68Ga-DOTA imaging.ResultsGLP-1r binding potential in the obese pancreas was reduced by 75% compared with lean animals. Similar reductions were evident for fat tissue, but not for the duodenum. In the lean group, induced hyperinsulinemia reduced pancreatic GLP-1r density to a level comparable with that of the obese group. The reduction in blood to tissue transfer of the GLP-1r ligand paralleled that of tissue perfusion estimated using 68Ga-DOTA.ConclusionsThese observations establish that a reduction in abdominal tissue perfusion and a lower GLP-1r density account for the diminished insulinotropic effect of GLP-1 agonists in type 2 diabetes.

scholarly journals Improved Models for Plasma Radiometabolite Correction and their Impact on Kinetic Quantification in PET Studies

2015 ◽  
Vol 35 (9) ◽  
pp. 1462-1469 ◽  
Author(s):  
Matteo Tonietto ◽  
Mattia Veronese ◽  
Gaia Rizzo ◽  
Paolo Zanotti-Fregonara ◽  
Talakad G Lohith ◽  
...  
Keyword(s):  
Model Misspecification ◽  
Simulated Data ◽  
Input Function ◽  
Volume Of Distribution ◽  
Binding Potential ◽  
Weighted Residuals ◽  
Injection Duration ◽  
Positron Emission ◽  
Reliable Quantification ◽  
The Impact

The quantification of dynamic positron emission tomography studies performed with arterial sampling usually requires correcting the input function for the presence of radiometabolites by using a model of the plasma parent fraction (PPf). Here, we show how to include the duration of radioligand injection in the PPf model formulations to achieve a more physiologic description of the plasma measurements. This formulation (here called convoluted model) was tested on simulated data and on three datasets with different parent kinetics: [11C]NOP-1A, [11C]MePPEP, and [11C](R)-rolipram. Results showed that convoluted PPf models better described the fraction of unchanged parent in the plasma compared with standard models for all three datasets (weighted residuals sum of squares up to 25% lower). When considering the effect on tissue quantification, the overall impact on the total volume of distribution (VT) was low. However, the impact was significant and radioligand-dependent on the binding potential (BP) and the microparameters ( K1, k2, k3, and k4). Simulated data confirmed that quantification is sensitive to different degrees to PPf model misspecification. Including the injection duration allows obtaining a more accurate correction of the input function for the presence of radiometabolites and this yields a more reliable quantification of the tissue parameters.

scholarly journals µ-Opioid Activity in Chronic TMD Pain Is Associated with COMT Polymorphism

2019 ◽  
Vol 98 (12) ◽  
pp. 1324-1331 ◽  
Author(s):  
T.D. Nascimento ◽  
N. Yang ◽  
D. Salman ◽  
H. Jassar ◽  
N. Kaciroti ◽  
...  
Keyword(s):  
Chronic Pain ◽  
Resting State ◽  
Pain Sensitivity ◽  
Temporomandibular Disorder ◽  
Late Phase ◽  
Binding Potential ◽  
Genetic Profile ◽  
Comt Genotype ◽  
Positron Emission ◽  
The Impact

Clinicians have the dilemma of prescribing opioid or nonopioid analgesics to chronic pain patients; however, the impact of pain on our endogenous µ-opioid system and how our genetic profile (specifically catechol-O-methyltransferase [ COMT] polymorphisms) impacts its activation are currently unknown. Twelve chronic temporomandibular disorder (TMD) patients and 12 healthy controls (HCs) were scanned using positron emission tomography (PET) with [11C]carfentanil, a selective radioligand for µ-opioid receptors (µORs). The first 45 min of each PET measured the µOR nondisplaceable binding potential (BPND) at resting state, and the last 45 min consisted of a 20-min masseteric pain challenge with an injection of 5% hypertonic saline. Participants were also genotyped for different COMT alleles. There were no group differences in µOR BPND at resting state (early phase). However, during the masseteric pain challenge (late phase), TMD patients exhibited significant reductions in µOR BPND (decreased [11C]carfentanil binding) in the contralateral parahippocampus ( P = 0.002) compared to HCs. The µOR BPND was also significantly lower in TMD patients with longer pain chronicity ( P < 0.001). When considering COMT genotype and chronic pain suffering, TMD patients with the COMT 158Met substitution had higher pain sensitivity and longer pain chronicity with a 5-y threshold for µOR BPND changes to occur in the parahippocampus. Together, the TMD diagnosis, COMT 158Met substitution, and pain chronicity explained 52% of µOR BPND variance in the parahippocampus (cumulative R2 = 52%, P < 0.003, and HC vs. TMD Cohen’s effect size d = 1.33 SD). There is strong evidence of dysregulation of our main analgesic and limbic systems in chronic TMD pain. The data also support precision medicine by helping identify TMD patients who may be more susceptible to chronic pain sensitivity and opioid dysfunction based on their genetic profile.

The impact of stereotactic pallidal surgery on the dopamine D2 receptor in Parkinson disease: a positron emission tomography study

2003 ◽  
Vol 98 (1) ◽  
pp. 57-63 ◽  
Author(s):  
Takeshi Nakajima ◽  
Taro Nimura ◽  
Keiichiro Yamaguchi ◽  
Tadashi Ando ◽  
Masatoshi Itoh ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Parkinson Disease ◽  
Receptor Binding ◽  
Emission Tomography ◽  
Binding Potential ◽  
Yahr Stage ◽  
Content Type ◽  
Positron Emission ◽  
The Impact ◽  
Fine Print

Object. The aim of this study was to estimate the impact of stereotactic pallidal surgery on the binding potential of dopamine D2 receptors in patients with advanced Parkinson disease (PD). Methods. Six patients with advanced PD (three men and three women; mean age 56.7 ± 9.8 years, Hoehn and Yahr stage 3.3 ± 1.1/3.9 ± 1.2 [on/off scores], mean ± standard deviation) underwent stereotactic pallidal surgery. One underwent right posteroventral pallidotomy (PVP), one received left PVP, three were treated with deep brain stimulation (DBS) of the left globus pallidus internus (GPi), and one with bilateral DBS of the GPi. The binding potential of the dopamine D2 receptors of these patients was determined before and after surgery by using positron emission tomography scanning with 11C-nemonapride and it was compared with the value in eight healthy volunteers. The authors also examined whether changes in the D2 receptor binding potential were correlated with the clinical outcome. The clinical symptoms, especially those in the off state, were significantly improved after surgery. Preoperatively, the D2 receptor binding potential in the putamen was elevated by 27% (p < 0.01) and that in the thalamus was 29% lower than that in controls (p < 0.01). The D2 receptor binding potential in the putamen and thalamus returned to control levels after surgery. The preoperative level of the D2 receptor binding potential in the anterior cingulate cortex was comparable to that of controls, but it declined significantly after surgery, whereas the D2 receptor binding potential in other regions of both hemispheres showed no significant changes after surgery. Although the D2 receptor binding potential did not correlate with the Hoehn and Yahr stage, the Schwab and England score, or the Unified PD Rating Scale (UPDRS) score, a positive correlation was seen between the percent improvement rate of the total UPDRS score in the off state and the percentage change of the D2 receptor binding potential in the putamen (r = 0.773, p = 0.0417 according to the Pearson linear correlation). Conclusions. The altered dopamine D2 receptor binding potential in the putamen might play a crucial role in clinical improvement after PVP or DBS of the GPi in advanced PD.

scholarly journals Intravenous Ethanol Increases Dopamine Release in the Ventral Striatum in Humans: PET Study Using Bolus-Plus-Infusion Administration of [11C]raclopride

2015 ◽  
Vol 35 (3) ◽  
pp. 424-431 ◽  
Author(s):  
Sargo Aalto ◽  
Kimmo Ingman ◽  
Kati Alakurtti ◽  
Valtteri Kaasinen ◽  
Jussi Virkkala ◽  
...  
Keyword(s):  
Ventral Striatum ◽  
Region Of Interest ◽  
Pet Scan ◽  
Binding Potential ◽  
Time Interval ◽  
Ethanol Infusion ◽  
Positron Emission ◽  
The Difference ◽  
Male Subjects ◽  
Da Release

Ethanol increases the interstitial dopamine (DA) concentration in the nucleus accumbens (NAcc) of experimental animals, but positron emission tomography (PET) studies using the single-bolus protocol of the [11C]-raclopride competition paradigm have yielded conflicting results in humans. To resolve disparate previous findings, we utilized the bolus-plus-infusion (B/I) method, allowing both baseline and intervention quantification of [11C]raclopride binding during a single 105-minute PET scan, to investigate possible ethanol-induced DA release in nine healthy male subjects. A 25-minute intravenous ethanol (7.6%) infusion, resulting in a 1.3 g/L mean blood ethanol concentration, was administered using masked timing during the PET scan. Automated region-of-interest analysis testing the difference between baseline (40–50 minutes) and intervention (60–85 minutes) revealed an average 12.6% decrease in [11C]raclopride binding in the ventral striatum (VST, P=0.003) including the NAcc. In addition, a shorter time interval from the start of ethanol infusion to the first subjective effect was associated with a greater binding potential decrease bilaterally in the VST ( r=0.92, P=0.004), and the feeling of pleasure was associated with a decrease in binding potential values in both the caudate nucleus ( r=−0.87, P=0.003) and putamen ( r=−0.74; P=0.02). These results confirm that ethanol induces rapid DA release in the limbic striatum, which can be reliably estimated using the B/I method in one imaging session.

scholarly journals Cerebellar heterogeneity and its impact on PET data quantification of 5-HT receptor radioligands

2017 ◽  
Vol 37 (9) ◽  
pp. 3243-3252 ◽  
Author(s):  
Melanie Ganz ◽  
Ling Feng ◽  
Hanne Demant Hansen ◽  
Vincent Beliveau ◽  
Claus Svarer ◽  
...  
Keyword(s):  
Regional Differences ◽  
Binding Potential ◽  
Reference Tissue ◽  
Tissue Modeling ◽  
Standardized Uptake Values ◽  
Positron Emission ◽  
Serotonin System ◽  
Signed Rank ◽  
The Impact ◽  
G Protein Coupled

In the quantification of positron emission tomography (PET) radiotracer binding, a commonly used method is reference tissue modeling (RTM). RTM necessitates a proper reference and a ubiquitous choice for G-protein coupled receptors is the cerebellum. We investigated regional differences in uptake within the grey matter of the cerebellar hemispheres (CH), the cerebellar white matter (CW), and the cerebellar vermis (CV) for five PET radioligands targeting the serotonin system. Furthermore, we evaluated the impact of choosing different reference regions when quantifying neocortical binding. The PET and MR images are part of the Cimbi database: 5-HT1AR ([11C]CUMI-101, n = 8), 5-HT1BR ([11C]AZ10419369, n = 36), 5-HT2AR ([11C]Cimbi-36, n = 29), 5-HT4R ([11C]SB207145, n = 59), and 5-HTT ([11C]DASB, n = 100). We employed SUIT and FreeSurfer to delineate CV, CW, and CH and quantified mean standardized uptake values (SUV) and nondisplaceable neocortical binding potential (BPND). Statistical difference was assessed with paired nonparametric two-sided Wilcoxon signed-rank tests and multiple comparison corrected via false discovery rate. We demonstrate significant radioligand specific regional differences in cerebellar uptake. These differences persist when using different cerebellar regions for RTM, but the influence on the neocortical BPND is small. Nevertheless, our data highlight the importance of validating each radioligand carefully for defining the optimal reference region.

VLSI Design for Functional Failure Analysis in the < 90 nm and Flip-Chip Era

2003 ◽  
Author(s):  
Yoav Weizman ◽  
Ezra Baruch
Keyword(s):  
Failure Analysis ◽  
Flip Chip ◽  
Light Emission ◽  
Vlsi Design ◽  
Optical Resolution ◽  
Critical Issue ◽  
Acquisition Time ◽  
Resolution Limit ◽  
Design Rules ◽  
The Impact

Abstract In recent years, two new techniques were introduced for flip chip debug; the Laser Voltage Probing (LVP) technique and Time Resolved Light Emission Microscopy (TRLEM). Both techniques utilize the silicon’s relative transparency to wavelengths longer than the band gap. This inherent wavelength limitation, together with the shrinking dimensions of modern CMOS devices, limit the capabilities of these tools. It is known that the optical resolution limits of the LVP and TRLEM techniques are bounded by the diffraction limit which is ~1um for both tools using standard optics. This limitation was reduced with the addition of immersion lens optics. Nevertheless, even with this improvement, shrinking transistor geometry is leading to increased acquisition time, and the overlapping effect between adjacent nodes remains a critical issue. The resolution limit is an order of magnitude above the device feature densities in the &lt; 90nm era. The scaling down of transistor geometry is leading to the inevitable consequence where more than 50% of the transistors in 90nm process have widths smaller than 0.4um. The acquisition time of such nodes becomes unreasonably long. In order to examine nodes in a dense logic cuicuit, cross talk and convolution effects between neighboring signals also need to be considered. In this paper we will demonstrate the impact that these effects may have on modern design. In order to maintain the debug capability, with the currently available analytical tools for future technologies, conceptual modification of the FA process is required. This process should start on the IC design board where the VLSI designer should be familiar with FA constraints, and thus apply features that will enable enhanced FA capabilities to the circuit in hand during the electrical design or during the physical design stages. The necessity for reliable failure analysis in real-time should dictate that the designer of advanced VLSI blocks incorporates failure analysis constraints among other design rules. The purpose of this research is to supply the scientific basis for the optimal incorporation of design rules for optical probing in the &lt; 90nm gate era. Circuit designers are usually familiar with the nodes in the design which are critical for debug, and the type of measurement (logic or DC level) they require. The designer should enable the measurement of these signals by applying certain circuit and physical constraints. The implementation of these constraints may be done at the cell level, the block level or during the integration. We will discuss the solutions, which should be considered in order to mitigate tool limitations, and also to enable their use for next generation processes.

scholarly journals Time-to-Treatment in Oral Cancer: Causes and Implications for Survival

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1321
Author(s):  
Constanza Saka-Herrán ◽  
Enric Jané-Salas ◽  
Antoni Mari-Roig ◽  
Albert Estrugo-Devesa ◽  
José López-López
Keyword(s):  
Oral Cancer ◽  
Previous Treatment ◽  
Diagnostic Procedures ◽  
Original Data ◽  
Primary Treatment ◽  
Medical Attention ◽  
Time Interval ◽  
Pre Treatment ◽  
The Impact ◽  
Lack Of Knowledge

The purpose of this review was to identify and describe the causes that influence the time-intervals in the pathway of diagnosis and treatment of oral cancer and to assess its impact on prognosis and survival. The review was structured according to the recommendations of the Aarhus statement, considering original data from individual studies and systematic reviews that reported outcomes related to the patient, diagnostic and pre-treatment intervals. The patient interval is the major contributor to the total time-interval. Unawareness of signs and/or symptoms, denial and lack of knowledge about oral cancer are the major contributors to the process of seeking medical attention. The diagnostic interval is influenced by tumor factors, delays in referral due to higher number of consultations and previous treatment with different medicines or dental procedures and by professional factors such as experience and lack of knowledge related to the disease and diagnostic procedures. Patients with advanced stage disease, primary treatment with radiotherapy, treatment at an academic facility and transitions in care are associated with prolonged pre-treatment intervals. An emerging body of evidence supports the impact of prolonged pre-treatment and treatment intervals with poorer survival from oral cancer.

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