ResearchPad - positron-emission-tomography https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Direct comparison of activation maps during galvanic vestibular stimulation: A hybrid H<sub>2</sub>[<sup>15</sup> O] PET—BOLD MRI activation study]]> https://www.researchpad.co/article/elastic_article_14749 Previous unimodal PET and fMRI studies in humans revealed a reproducible vestibular brain activation pattern, but with variations in its weighting and expansiveness. Hybrid studies minimizing methodological variations at baseline conditions are rare and still lacking for task-based designs. Thus, we applied for the first time hybrid 3T PET-MRI scanning (Siemens mMR) in healthy volunteers using galvanic vestibular stimulation (GVS) in healthy volunteers in order to directly compare H215O-PET and BOLD MRI responses. List mode PET acquisition started with the injection of 750 MBq H215O simultaneously to MRI EPI sequences. Group-level statistical parametric maps were generated for GVS vs. rest contrasts of PET, MR-onset (event-related), and MR-block. All contrasts showed a similar bilateral vestibular activation pattern with remarkable proximity of activation foci. Both BOLD contrasts gave more bilateral wide-spread activation clusters than PET; no area showed contradictory signal responses. PET still confirmed the right-hemispheric lateralization of the vestibular system, whereas BOLD-onset revealed only a tendency. The reciprocal inhibitory visual-vestibular interaction concept was confirmed by PET signal decreases in primary and secondary visual cortices, and BOLD-block decreases in secondary visual areas. In conclusion, MRI activation maps contained a mixture of CBF measured using H215O-PET and additional non-CBF effects, and the activation-deactivation pattern of the BOLD-block appears to be more similar to the H215O-PET than the BOLD-onset.

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<![CDATA[Neuroimaging modality fusion in Alzheimer’s classification using convolutional neural networks]]> https://www.researchpad.co/article/N4bce0426-e39d-45a0-9dc9-42db4f6cba04

Automated methods for Alzheimer’s disease (AD) classification have the potential for great clinical benefits and may provide insight for combating the disease. Machine learning, and more specifically deep neural networks, have been shown to have great efficacy in this domain. These algorithms often use neurological imaging data such as MRI and FDG PET, but a comprehensive and balanced comparison of the MRI and amyloid PET modalities has not been performed. In order to accurately determine the relative strength of each imaging variant, this work performs a comparison study in the context of Alzheimer’s dementia classification using the Alzheimer’s Disease Neuroimaging Initiative (ADNI) dataset with identical neural network architectures. Furthermore, this work analyzes the benefits of using both modalities in a fusion setting and discusses how these data types may be leveraged in future AD studies using deep learning.

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<![CDATA[Exploit fully automatic low-level segmented PET data for training high-level deep learning algorithms for the corresponding CT data]]> https://www.researchpad.co/article/5c8823d0d5eed0c484639091

We present an approach for fully automatic urinary bladder segmentation in CT images with artificial neural networks in this study. Automatic medical image analysis has become an invaluable tool in the different treatment stages of diseases. Especially medical image segmentation plays a vital role, since segmentation is often the initial step in an image analysis pipeline. Since deep neural networks have made a large impact on the field of image processing in the past years, we use two different deep learning architectures to segment the urinary bladder. Both of these architectures are based on pre-trained classification networks that are adapted to perform semantic segmentation. Since deep neural networks require a large amount of training data, specifically images and corresponding ground truth labels, we furthermore propose a method to generate such a suitable training data set from Positron Emission Tomography/Computed Tomography image data. This is done by applying thresholding to the Positron Emission Tomography data for obtaining a ground truth and by utilizing data augmentation to enlarge the dataset. In this study, we discuss the influence of data augmentation on the segmentation results, and compare and evaluate the proposed architectures in terms of qualitative and quantitative segmentation performance. The results presented in this study allow concluding that deep neural networks can be considered a promising approach to segment the urinary bladder in CT images.

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<![CDATA[Brief communication: β-cell function influences dopamine receptor availability]]> https://www.researchpad.co/article/5c8c1952d5eed0c484b4d3f2

We aim to identify physiologic regulators of dopamine (DA) signaling in obesity but previously did not find a compelling relationship with insulin sensitivity measured by oral-minimal model (OMM) and DA subtype 2 and 3 receptor (D2/3R) binding potential (BPND). Reduced disposition index (DI), a β-cell function metric that can also be calculated by OMM, was shown to predict a negative reward behavior that occurs in states of lower endogenous DA. We hypothesized that reduced DI would occur with higher D2/3R BPND, reflecting lower endogenous DA. Participants completed PET scanning, with a displaceable radioligand to measure D2/3R BPND, and a 5-hour oral glucose tolerance test to measure DI by OMM. We studied 26 age-similar females without (n = 8) and with obesity (n = 18) (22 vs 39 kg/m2). Reduced DI predicted increased striatal D2/3R BPND independent of BMI. By accounting for β-cell function, we were able to determine that the state of insulin and glucose metabolism is pertinent to striatal D2/3R BPND in obesity.

Clinical Trial Registration Number: NCT00802204

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<![CDATA[RaCaT: An open source and easy to use radiomics calculator tool]]> https://www.researchpad.co/article/5c76fe64d5eed0c484e5b9d0

Purpose

The widely known field ‘Radiomics’ aims to provide an extensive image based phenotyping of e.g. tumors using a wide variety of feature values extracted from medical images. Therefore, it is of utmost importance that feature values calculated by different institutes follow the same feature definitions. For this purpose, the imaging biomarker standardization initiative (IBSI) provides detailed mathematical feature descriptions, as well as (mathematical) test phantoms and corresponding reference feature values. We present here an easy to use radiomic feature calculator, RaCaT, which provides the calculation of a large number of radiomic features for all kind of medical images which are in compliance with the standard.

Methods

The calculator is implemented in C++ and comes as a standalone executable. Therefore, it can be easily integrated in any programming language, but can also be called from the command line. No programming skills are required to use the calculator. The software architecture is highly modularized so that it is easily extendible. The user can also download the source code, adapt it if needed and build the calculator from source. The calculated feature values are compliant with the ones provided by the IBSI standard. Source code, example files for the software configuration, and documentation can be found online on GitHub (https://github.com/ellipfaehlerUMCG/RaCat).

Results

The comparison with the standard values shows that all calculated features as well as image preprocessing steps, comply with the IBSI standard. The performance is also demonstrated on clinical examples.

Conclusions

The authors successfully implemented an easy to use Radiomics calculator that can be called from any programming language or from the command line. Image preprocessing and feature settings and calculations can be adjusted by the user.

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<![CDATA[In vivo positron emission tomographic blood pool imaging in an immunodeficient mouse model using 18F-fluorodeoxyglucose labeled human erythrocytes]]> https://www.researchpad.co/article/5c57e690d5eed0c484ef3751

99m-Technetium-labeled (99mTc) erythrocyte imaging with planar scintigraphy is widely used for evaluating both patients with occult gastrointestinal bleeding and patients at risk for chemotherapy-induced cardiotoxicity. While a number of alternative radionuclide-based blood pool imaging agents have been proposed, none have yet to achieve widespread clinical use. Here, we present both in vitro and small animal in vivo imaging evidence that the high physiological expression of the glucose transporter GLUT1 on human erythrocytes allows uptake of the widely available radiotracer 2-deoxy-2-(18F)fluoro-D-glucose (FDG), at a rate and magnitude sufficient for clinical blood pool positron emission tomographic (PET) imaging. This imaging technique is likely to be amenable to rapid clinical translation, as it can be achieved using a simple FDG labeling protocol, requires a relatively small volume of phlebotomized blood, and can be completed within a relatively short time period. As modern PET scanners typically have much greater count detection sensitivities than that of commonly used clinical gamma scintigraphic cameras, FDG-labeled human erythrocyte PET imaging may not only have significant advantages over 99mTc-labeled erythrocyte imaging, but may have other novel blood pool imaging applications.

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<![CDATA[Activity painting: PET images of freely defined activity distributions applying a novel phantom technique]]> https://www.researchpad.co/article/5c57e684d5eed0c484ef3523

The aim of this work was to develop a novel phantom that supports the construction of highly reproducible phantoms with arbitrary activity distributions for PET imaging. It could offer a methodology for answering questions related to texture measurements in PET imaging. The basic idea is to move a point source on a 3-D trajectory in the field of view, while continuously acquiring data. The reconstruction results in a 3-D activity concentration map according to the pathway of the point source. A 22Na calibration point source was attached to a high precision robotic arm system, where the 3-D movement was software controlled. 3-D activity distributions of a homogeneous cube, a sphere, a spherical shell and a heart shape were simulated. These distributions were used to measure uniformity and to characterize reproducibility. Two potential applications using the lesion simulation method are presented: evaluation in changes of textural properties related to the position in the PET field of view; scanner comparison based on visual and quantitative evaluation of texture features. A lesion with volume of 50x50x50 mm3 can be simulated during approximately 1 hour. The reproducibility of the movement was found to be >99%. The coefficients of variation of the voxels within a simulated homogeneous cube was 2.34%. Based on 5 consecutive and independent measurements of a 36 mm diameter hot sphere, the coefficient of variation of the mean activity concentration was 0.68%. We obtained up to 18% differences within the values of investigated textural indexes, when measuring a lesion in different radial positions of the PET field of view. In comparison of two different human PET scanners the percentage differences between heterogeneity parameters were in the range of 5–55%. After harmonizing the voxel sizes this range reduced to 2–16%. The general activity distributions provided by the two different vendor show high similarity visually. For the demonstration of the flexibility of this method, the same pattern was also simulated on a small animal PET scanner giving similar results, both quantitatively and visually. 3-D motion of a point source in the PET field of view is capable to create an irregular shaped activity distribution with high reproducibility.

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<![CDATA[Comparison of the binding of the gastrin-releasing peptide receptor (GRP-R) antagonist 68Ga-RM2 and 18F-FDG in breast cancer samples]]> https://www.researchpad.co/article/5c478c7dd5eed0c484bd29e8

The Gastrin-Releasing Peptide Receptor (GRPR) is over-expressed in estrogen receptor (ER) positive breast tumors and related metastatic lymph nodes offering the opportunity of imaging and therapy of luminal tumors. 68Ga-RM2 binding and 18F-FDG binding in tumoral zones were measured and compared using tissue micro-imaging with a beta imager on 14 breast cancer samples (10 primaries and 4 associated metastatic lymph nodes). Results were then assessed against ER expression, progesterone receptor (PR) expression, HER2 over-expression or not and Ki-67 expression. GRPR immunohistochemistry (IHC) was also performed on all samples. We also retrospectively compared 68Ga-RM2 and 18F-FDG bindings to 18F-FDG SUVmax on the pre-therapeutic PET/CT examination, if available. 68Ga-RM2 binding was significantly higher in tumors expressing GRPR on IHC than in GRPR-negative tumors (P = 0.022). In ER+ tumors, binding of 68Ga-RM2 was significantly higher than 18F-FDG (P = 0.015). In tumors with low Ki-67, 68Ga-RM2 binding was also significantly increased compared to 18F-FDG (P = 0.029). Overall, the binding of 68Ga-RM2 and 18F-FDG displayed an opposite pattern in tumor samples and 68Ga-RM2 binding was significantly higher in tumors that had low 18F-FDG binding (P = 0.021). This inverse correlation was also documented in the few patients in whom a 18F-FDG PET/CT examination before surgery was available. Findings from this in vitro study suggest that GRPR targeting can be an alternative to 18F-FDG imaging in ER+ breast tumors. Moreover, because GRPR antagonists can also be labeled with lutetium-177 this opens new avenues for targeted radionuclide therapy in the subset of patients with progressive metastatic disease following conventional treatments.

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<![CDATA[Relative cerebral flow from dynamic PIB scans as an alternative for FDG scans in Alzheimer’s disease PET studies]]> https://www.researchpad.co/article/5c605a60d5eed0c4847ccf3a

In Alzheimer’s Disease (AD) dual-tracer positron emission tomography (PET) studies with 2-[18F]-fluoro-2-deoxy-D-glucose (FDG) and 11C-labelled Pittsburgh Compound B (PIB) are used to assess metabolism and cerebral amyloid-β deposition, respectively. Regional cerebral metabolism and blood flow (rCBF) are closely coupled, both providing an index for neuronal function. The present study compared PIB-derived rCBF, estimated by the ratio of tracer influx in target regions relative to reference region (R1) and early-stage PIB uptake (ePIB), to FDG scans. Fifteen PIB positive (+) patients and fifteen PIB negative (-) subjects underwent both FDG and PIB PET scans to assess the use of R1 and ePIB as a surrogate for FDG. First, subjects were classified based on visual inspection of the PIB PET images. Then, discriminative performance (PIB+ versus PIB-) of rCBF methods were compared to normalized regional FDG uptake. Strong positive correlations were found between analyses, suggesting that PIB-derived rCBF provides information that is closely related to what can be seen on FDG scans. Yet group related differences between method’s distributions were seen as well. Also, a better correlation with FDG was found for R1 than for ePIB. Further studies are needed to validate the use of R1 as an alternative for FDG studies in clinical applications.

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<![CDATA[Clinical efficacy and cost-effectiveness of endobronchial ultrasound-guided transbronchial needle aspiration for preoperative staging of non-small–cell lung cancer: Results of a French prospective multicenter trial (EVIEPEB)]]> https://www.researchpad.co/article/5c3d0157d5eed0c48403a6dd

This two-step study evaluated the cost-effectiveness of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) for presurgery staging of non-small cell lung cancer (NSCLC) in France (EVIEPEB; ClinicalTrial.gov identifier NCT00960271).

Step 1 consisted of a high-benchmark EBUS-TBNA–training program in participating hospital centers. Step 2 was a prospective, national, multicenter study on patients with confirmed or suspected NSCLC and an indication for mediastinal staging with at least one lymph node > 1 cm in diameter. Patients with negative or uninformative EBUS-TBNA and positron-emission tomography-positive or -negative nodes, respectively, underwent either mediastinoscopy or surgery. Direct costs related to final diagnosis of node status were prospectively recorded.

Sixteen of 22 participating centers were certified by the EBUS-TBNA–training program and enrolled 163 patients in Step 2. EBUS-TBNA was informative for 149 (91%) patients (75 malignant, 74 non-malignant) and uninformative for 14 (9%). Mediastinoscopy was avoided for 80% of the patients. With a 52% malignant-node rate, EBUS-TBNA positive- and negative-predictive values, respectively, were 100% and 90%. EBUS-TBNA was cost-effective, with expected savings of €1,450 per patient, and would have remained cost-effective even if all EBUS-TBNAs had been performed under general anesthesia or the cost of the procedure had been 30% higher (expected cost-saving of €994 and €1,427 per patient, respectively).

After EBUS-TBNA training and certification of participating centers, the results of this prospective multicenter study confirmed EBUS-TBNA cost-effectiveness for NSCLC staging.

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<![CDATA[Post-chemoradiotherapy FDG PET with qualitative interpretation criteria for outcome stratification in esophageal squamous cell carcinoma]]> https://www.researchpad.co/article/5c3d0175d5eed0c48403b89e

Objectives

Post-chemoradiotherapy (CRT) FDG PET is a useful prognosticator of esophageal cancer. However, debate on the diverse criteria of previous publications preclude worldwide multicenter comparisons, and even a universal practice guide. We aimed to validate a simple qualitative interpretation criterion of post-CRT FDG PET for outcome stratification and compare it with other criteria.

Methods

The post-CRT FDG PET of 114 patients with esophageal squamous cell carcinoma (ESCC) were independently interpreted using a qualitative 4-point scale (Qual4PS) that identified focal esophageal FDG uptake greater than liver uptake as residual tumor. Cohen’s κ coefficient (κ) was used to measure interobserver agreement of Qual4PS. The Kaplan-Meier method and Cox proportional hazards regression analyses were used for survival analysis. Other criteria included a different qualitative approach (QualBK), maximal standardized uptake values (SUVmax3.4, SUVmax2.5), relative change of SUVmax between pre- and post-CRT FDG PET (ΔSUVmax), mean standardized uptake values (SUVmean), metabolic volume (MV) and total lesion glycolysis (TLG).

Results

Overall interobserver agreement on the Qual4PS criterion was excellent (κ: 0.95). Except the QualBK, SUVmax2.5, and TLG, all the other criteria were significant predictors for overall survival (OS). Multivariable analysis showed only Qual4PS (HR: 15.41; P = 0.005) and AJCC stage (HR: 2.47; P = 0.007) were significant independent variables. The 2-year OS rates of Qual4PS(‒) patients undergoing CRT alone (68.4%) and patients undergoing trimodality therapy (62.5%) were not significant different, but the 2-year OS rates of Qual4PS(+) patients undergoing CRT alone (10.0%) were significantly lower than in patients undergoing trimodality therapy (42.1%).

Conclusions

The Qual4PS criterion is reproducible for assessing the response of ESCC to CRT, and valuable for predicting survival. It may add value to response-adapted treatment for ESCC patients, and help to decide whether surgery is warranted after CRT.

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<![CDATA[Accurate, robust and harmonized implementation of morpho-functional imaging in treatment planning for personalized radiotherapy]]> https://www.researchpad.co/article/5c3fa589d5eed0c484ca5858

In this work we present a methodology able to use harmonized PET/CT imaging in dose painting by number (DPBN) approach by means of a robust and accurate treatment planning system. Image processing and treatment planning were performed by using a Matlab-based platform, called CARMEN, in which a full Monte Carlo simulation is included. Linear programming formulation was developed for a voxel-by-voxel robust optimization and a specific direct aperture optimization was designed for an efficient adaptive radiotherapy implementation. DPBN approach with our methodology was tested to reduce the uncertainties associated with both, the absolute value and the relative value of the information in the functional image. For the same H&N case, a single robust treatment was planned for dose prescription maps corresponding to standardized uptake value distributions from two different image reconstruction protocols: One to fulfill EARL accreditation for harmonization of [18F]FDG PET/CT image, and the other one to use the highest available spatial resolution. Also, a robust treatment was planned to fulfill dose prescription maps corresponding to both approaches, the dose painting by contour based on volumes and our voxel-by-voxel DPBN. Adaptive planning was also carried out to check the suitability of our proposal.

Different plans showed robustness to cover a range of scenarios for implementation of harmonizing strategies by using the highest available resolution. Also, robustness associated to discretization level of dose prescription according to the use of contours or numbers was achieved. All plans showed excellent quality index histogram and quality factors below 2%. Efficient solution for adaptive radiotherapy based directly on changes in functional image was obtained. We proved that by using voxel-by-voxel DPBN approach it is possible to overcome typical drawbacks linked to PET/CT images, providing to the clinical specialist confidence enough for routinely implementation of functional imaging for personalized radiotherapy.

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<![CDATA[Prognostic value of baseline metabolic tumor volume and total lesion glycolysis in patients with lymphoma: A meta-analysis]]> https://www.researchpad.co/article/5c3fa583d5eed0c484ca53ef

Whether baseline metabolic tumor volume (TMTV) and total lesion glycolysis (TLG) measured by FDG-PET/CT affected prognosis of patients with lymphoma was controversial. We searched PubMed, EMBASE and Cochrane to identify studies assessing the effect of baseline TMTV and TLG on the survival of lymphoma patients. Pooled hazard ratios (HR) for overall survival (OS) and progression-free survival (PFS) were calculated, along with 95% confidence intervals (CI). Twenty-seven eligible studies including 2,729 patients were analysed. Patients with high baseline TMTV showed a worse prognosis with an HR of 3.05 (95% CI 2.55–3.64, p<0.00001) for PFS and an HR of 3.07 (95% CI 2.47–3.82, p<0.00001) for OS. Patients with high baseline TLG also showed a worse prognosis with an HR of 3.44 (95% CI 2.37–5.01, p<0.00001) for PFS and an HR of 3.08 (95% CI 1.84–5.16, p<0.00001) for OS. A high baseline TMTV was significantly associated with worse survival in DLBCL patients treated with R-CHOP (OS, pooled HR = 3.52; PFS, pooled HR = 2.93). A high baseline TLG was significantly associated with worse survival in DLBCL patients treated with R-CHOP (OS, pooled HR = 3.06; PFS, pooled HR = 2.93). The negative effect of high baseline TMTV on PFS was demonstrated in HL (pooled HR = 3.89). A high baseline TMTV was significantly associated with worse survival in ENKL patients (OS, pooled HR = 2.24; PFS, pooled HR = 3.25). A high baseline TLG was significantly associated with worse survival in ENKL patients (OS, pooled HR = 2.58; PFS, pooled HR = 2.99). High baseline TMTV or TLG predict significantly worse PFS and OS in patients with lymphoma. Future studies are warranted to explore whether TMTV or TLG could be integrated into various prognostic models for clinical decision making.

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<![CDATA[Gender as an independent prognostic factor in small-cell lung cancer: Inha Lung Cancer Cohort study using propensity score matching]]> https://www.researchpad.co/article/5c1966cdd5eed0c484b52ed9

Introduction

The prognostic relevance of gender is undetermined in patients with small-cell lung cancer (SCLC). Therefore, we investigated whether gender is a prognostic factor in a SCLC cohort after controlling for confounding factors.

Materials and methods

Fifteen prognostic factors were classified into four groups (patient, stage migration, tumor, and treatment). The prognostic relevance of gender was evaluated using propensity score matching, Cox proportional hazards regression, and stepwise fashion adjustments.

Results

Of 591 patients with SCLC, 88 were women (14.9%). Women were more likely than men to have no history of smoking (48.9% vs. 2.0%, P < 0.001) and limited disease (48.9% vs. 37.8%, P = 0.050). Women had less progressive disease in M stage than men (52.3% vs. 62.8%, P = 0.031). Women had better survival than men in the entire cohort (median survival times [MSTs] and 95% confidence intervals [CIs]: 9.7 months and 7.8–11.6 for women, 8.0 months and 7.0–8.9 for men, log-rank P = 0.034) and in the matched cohort (MSTs and 95% CIs: 8.8 months and 5.8–11.8 for women, 5.9 months and 4.5–7.4 for men, log-rank P = 0.013). Female gender was a prognostic factor predicting better survival, even after stepwise and full adjustment with all prognostic variables (adjusted hazard ratios and 95% CIs: 0.51 and 0.34–0.77, P = 0.001 for entire cohort, 0.42 and 0.24–0.75, P = 0.003 for matched cohort).

Conclusions

Our results confirmed that gender is an independent prognostic factor in patients with SCLC.

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<![CDATA[Longer TOMM40 poly-T variants associated with higher FDDNP-PET medial temporal tau and amyloid binding]]> https://www.researchpad.co/article/5c117bdfd5eed0c48469abab

Background

The translocase of outer mitochondrial membrane 40 (TOMM40), which lies in linkage disequilibrium with the apolipoprotein E (APOE) gene, has been implicated in Alzheimer’s disease (AD). TOMM40 influences AD pathology through mitochondrial neurotoxicity, and the medial temporal lobe (MTL) is the most likely brain region for identifying early manifestations of AD-related morphology changes. While early reports indicated that the longer length poly-T allele of TOMM40 increases risk for AD, these findings have not been consistently replicated in further studies. We examined the effect of TOMM40 and APOE on regional brain positron emission tomography (PET) 2-(1-{6-[(2 [F18]fluoroethyl) (methyl) amino]-2-naphthyl}ethylidene)malononitrile (FDDNP) binding values in MTL.

Methods

A total of 73 non-demented older adults (42 females; mean age: 62.9(10.9) completed genotyping for both APOE and TOMM40 and received FDDNP-PET scans. For TOMM40, the lengths of the poly-T sequence were classified as short (14–20 repeats; S), long (21–29 repeats, L) or very long (>29 repeats, VL). Using general linear models, we examined medial temporal lobe FDDNP binding and cognitive functioning between TOMM40 and APOE-4 groups, with age, sex, and education as covariates.

Results

Data from 30 individuals with APOE-4 and L TOMM40 poly-T length, 11 non E4 TOMM40 S/S, 14 non E4 TOMM40 S/VL and 13 non E4 TOMM40 VL/VL were analyzed. Medial temporal FDDNP binding differed significantly between TOMM40/APOE groups (F(3,62) = 3.3,p = .03). Participants with TOMM40 S/S exhibited significantly lower binding compared to TOMM40 S/VL and APOE-4 carriers. We did not find a significant relationship between TOMM40 poly-T lengths/APOE risk groups and cognitive functioning.

Conclusions

This is the first report to demonstrate a significant association between longer TOMM40 poly-T lengths and higher medial temporal plaque and tangle burden in non-demented older adults. Identifying biomarkers that are risk factors for AD will enhance our ability to identify subjects likely to benefit from novel AD treatments.

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<![CDATA[Deep learning and artificial intelligence in radiology: Current applications and future directions]]> https://www.researchpad.co/article/5c0ae472d5eed0c484589b6d ]]> <![CDATA[68Ga and 188Re Starch-Based Microparticles as Theranostic Tool for the Hepatocellular Carcinoma: Radiolabeling and Preliminary In Vivo Rat Studies]]> https://www.researchpad.co/article/5989da35ab0ee8fa60b86084

Purpose

This work aims to develop, validate and optimize the radiolabeling of Starch-Based Microparticles (SBMP) by 188Re and 68Ga in the form of ready-to-use radiolabeling kits, the ultimate goal being to obtain a unique theranostic vector for the treatment of Hepatocellular Carcinoma.

Methods

Optimal labeling conditions and composition of freeze-dried kits were defined by monitoring the radiochemical purity while varying several parameters. In vitro stability studies were carried out, as well as an in vivo biodistribution as a preliminary approach with the intra-arterial injection of 68Ga radiolabeled SBMP into the hepatic artery of DENA-induced rats followed by PET/CT imaging.

Results

Kits were optimized for 188Re and 68Ga with high and stable radiochemical purity (>95% and >98% respectively). The in vivo preliminary study was successful with more than 95% of activity found in the liver and mostly in the tumorous part.

Conclusion

SBMP are a promising theranostic agent for the Selective Internal Radiation Therapy of Hepatocellular carcinoma.

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<![CDATA[Body Mass Index with Tumor 18F-FDG Uptake Improves Risk Stratification in Patients with Breast Cancer]]> https://www.researchpad.co/article/5989da55ab0ee8fa60b8eb9f

Purpose

To investigate the combined prognostic impact of body mass index (BMI) and tumor standardized uptake value (SUV) measured on pretreatment 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) in patients with breast cancer.

Methods

We evaluated a cohort of 332 patients with newly diagnosed breast cancer (stage I-III) who underwent pretreatment FDG PET/CT followed by curative resection. Patients were categorized as overweight (BMI ≥ 23 kg/m2) or normal weight (BMI < 23 kg/m2). Primary tumor maximum SUV was measured by FDG PET/CT. Associations between BMI and tumor SUV with disease recurrence were assessed using Cox regression models.

Results

Median follow-up was 39 months. There were 76 recurrences and 15 cancer-related deaths. Multivariable Cox regression analysis demonstrated that high tumor SUV (hazard ratio [HR] = 1.75; 95% CI, 1.02–3.02; P = 0.044) and overweight (HR = 1.84; 95% CI, 1.17–2.89; P = 0.008) were independent poor prognostic factors. Positive hormone receptor status was an independent predictor of favorable outcome (HR = 0.42; 95% CI, 0.26–0.68; P < 0.001). Overweight patients with high tumor SUV had a two-fold risk of recurrence compared to patients with normal weight or low tumor SUV after adjusting for clinical stage and tumor subtype (HR = 2.06; 95% CI, 1.30–3.27; P = 0.002).

Conclusions

In patients with breast cancer, higher tumor SUV was associated with a more adverse outcome particularly in overweight women. BMI status combined with tumor SUV data allows better risk-stratification of breast cancer, independent of clinical stage and tumor subtype.

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<![CDATA[Radioiodinated Exendin-4 Is Superior to the Radiometal-Labelled Glucagon-Like Peptide-1 Receptor Probes Overcoming Their High Kidney Uptake]]> https://www.researchpad.co/article/5989db44ab0ee8fa60bd7e64

GLP-1 receptors are ideal targets for preoperative imaging of benign insulinoma and for quantifying the beta cell mass. The existing clinical tracers targeting GLP-1R are all agonists with low specific activity and very high kidney uptake. In order to solve those issues we evaluated GLP-1R agonist Ex-4 and antagonist Ex(9–39) radioiodinated at Tyr40 side by side with [Nle14,Lys40(Ahx-DOTA-68Ga)NH2]Ex-4 (68Ga-Ex-4) used in the clinic. The Kd, Bmax, internalization and binding kinetics of [Nle14,125I-Tyr40-NH2]Ex-4 and [Nle14,125I-Tyr40-NH2]Ex(9–39) were studied in vitro using Ins-1E cells. Biodistribution and imaging studies were performed in nude mice bearing Ins-1E xenografts. In vitro evaluation demonstrated high affinity binding of the [Nle14,125I-Tyr40-NH2]Ex-4 agonist to the Ins-1E cells with fast internalization kinetics reaching a plateau after 30 min. The antagonist [Nle14,125I-Tyr40-NH2]Ex(9–39) did not internalize and had a 4–fold higher Kd value compared to the agonist. In contrast to [Nle14,125I-Tyr40-NH2]Ex(9–39), which showed low and transient tumor uptake, [Nle14,125I-Tyr40-NH2]Ex-4 demonstrated excellent in vivo binding properties with tumor uptake identical to that of 68Ga-Ex-4, but substantially lower kidney uptake resulting in a tumor-to-kidney ratio of 9.7 at 1 h compared to 0.3 with 68Ga-Ex-4. Accumulation of activity in thyroid and stomach for both peptides, which was effectively blocked by irenat, confirms that in vivo deiodination is the mechanism behind the low kidney retention of iodinated peptides. The 124I congener of [Nle14,125I-Tyr40-NH2]Ex-4 demonstrated a similar favourable biodistribution profile in the PET imaging studies in contrast to the typical biodistribution pattern of [Nle14,Lys40(Ahx-DOTA-68Ga)NH2]Ex-4. Our results demonstrate that iodinated Ex-4 is a very promising tracer for imaging of benign insulinomas. It solves the problem of high kidney uptake of the radiometal-labelled tracers by improving the tumor-to-kidney ratio measured for [Nle14,Lys40(Ahx-DOTA-68Ga)NH2]Ex-4 by 32 fold.

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<![CDATA[Investigation of 6-[18F]-Fluoromaltose as a Novel PET Tracer for Imaging Bacterial Infection]]> https://www.researchpad.co/article/5989da83ab0ee8fa60b9b4e9

Despite advances in the field of nuclear medicine, the imaging of bacterial infections has remained a challenge. The existing reagents suffer from poor sensitivity and specificity. In this study we investigate the potential of a novel PET (positron emission tomography) tracer that overcomes these limitations.

Methods

6-[18F]-fluoromaltose was synthesized. Its behavior in vitro was evaluated in bacterial and mammalian cultures. Detailed pharmacokinetic and biodistribution profiles for the tracer were obtained from a murine model.

Results

6-[18F]-fluoromaltose is taken up by multiple strains of pathogenic bacteria. It is not taken up by mammalian cancer cell lines. 6-[18F]-fluoromaltose is retained in infected muscles in a murine model of bacterial myositis. It does not accumulate in inflamed tissue.

Conclusion

We have shown that 6-[18F]-fluoromaltose can be used to image bacterial infection in vivo with high specificity. We believe that this class of agents will have a significant impact on the clinical management of patients.

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