Abstract 530: In vivo DVT Inflammation Presages Vein Wall Injury, and is Ameliorated by Statin Therapy

2017 ◽  
Vol 37 (suppl_1) ◽  
Author(s):  
Chase W Kessinger ◽  
Guanming Qi ◽  
Ahmed Tawakol ◽  
Peter K Henke ◽  
Farouc A Jaffer

Objective: Inflammation mediates early venous thrombosis (VT) resolution and can induce vein wall scarring (VWS), a key driver of the morbid post-thrombotic syndrome (PTS). Statins exhibit anti-inflammatory properties, and may positively impact VWS after VT. However, whether early inflammation contributes to this process and can be detected is not known. In this study, we hypothesized that early VT inflammation detected by 18F-fludeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) could predict subsequent VWS and that both VT inflammation and VWS would be attenuated by statin therapy. Methods: Stasis VT was induced by complete ligation in male C57BL/6J mice (n=55) in either the infrarenal inferior vena cava (IVC, n=42) or right jugular vein (n=13). IVC VT mice were randomized to statin or control groups. Statin (rosuvastatin 5mg/kg) was given by oral gavage starting one day prior to VT induction; control mice received PBS. All mice underwent survival FDG-PET/CT venography imaging on day 2. FDG-PET inflammation signals (standard uptake value (SUV), SUVmax, target-to-background ratios (TBR)) were measured. Picrosirius red staining of day 14 VT sections measured vein wall collagen/thickness. Ex vivo VT tissue gamma counting of a subgroup was performed at day 2. Whole-thrombus protein/mRNA and VT tissue sections assessed neutrophil content. Results: FDG-PET/CT at day 2 revealed increased FDG uptake in jugular VT over the contralateral sham surgery vein (p<0.001). Statin-treated mice showed a decrease in FDG-PET SUV, SUVmax and TBR (p<0.05 for all). Whole-thrombus analyses and tissue section immunostaining showed reduced thrombus neutrophil content at day 2, without reducing GLUT1 or MPO expression (p>0.05). At day 14, statin therapy significantly reduced VWS (p=0.02). In mice undergoing survival imaging, the day 2 FDG-PET VT inflammation signal correlated significantly with the magnitude of day 14 VWS (IVC VT r=0.74, p<0.001) and jugular models of VT (r=0.62, p=0.02). Conclusions: Quantitative FDG inflammation imaging demonstrates that early VT inflammation presages subsequent VWS, and is ameliorated by prophylactic statin therapy. The overall findings support the concept that statins and could reduce VWS and PTS.

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Chase W Kessinger ◽  
Ahmed Tawakol ◽  
Gregory R Wojtkiewicz ◽  
Peter K Henke ◽  
Ralph Weissleder ◽  
...  

Objective: While venous thrombosis (VT)-induced inflammation facilitates thrombus resolution, inflammation causes vein wall scarring (VWS). Recently, statins have shown to improve VT resolution and reduce VT inflammatory components. In this study, we hypothesized that early VT inflammation detected by 18F-FDG positron emission tomography/computed tomography (PET/CT) could predict subsequent late stage VWS, and would be attenuated by statin therapy. Methods: Stasis VT was induced in 8-12 week old male C57BL/6 mice (n=31) in either the right jugular vein (n=13) or inferior vena cava (IVC,n=18). Animals in the IVC VT cohort were randomized to statin (n=8) or control (n=10) treatment. Statin, rosuvastatin (5mg/kg), was administered by oral gavage, daily starting 24 hours prior to VT induction; control mice received saline. All mice underwent survival FDG-PET/CT venography imaging on day 2. FDG inflammation signals (standard uptake value=SUV) were measured in the thrombosed vein and compared to the sham-operated venous segments or treatment control. On day 14, mice were sacrificed and VT tissue was resected. Picrosirius red staining allowed measurement of collagen and vein wall thickness in VT sections. Results: FDG-PET/CT at day 2 revealed increased inflammation signal activity in jugular VT (SUV 1.43 ± 0.3 VT vs. 0.81 ± 0.3 contralateral vein, p<0.0001). Statin-treated mice showed a trend of decreased inflammation signal at day 2 in the IVC VT models (SUV 1.02 ± 0.1 statin VT vs. 1.42 ± 0.2 control VT, p=0.07). Day 14 histological analysis revealed significantly reduced vein wall injury in statin-treated animals (thickness, 32±9.4 μm statin; vs. 56.2±14.7 μm control, p=0.02). Day 2 FDG-PET inflammation in VT correlated positively with the magnitude of day 14 VWS (jugular VT, Spearman r=0.62, p=0.02; IVC VT r=0.74, p<0.001, respectively). Conclusions: Quantitative FDG-PET/CT imaging demonstrates that early in vivo VT inflammation predicts subsequent VWS, a driver of post-thrombotic syndrome (PTS). The overall findings strengthen: (i) the link between inflammation and PTS; (ii) the translational potential of FDG-PET inflammation to predict VWS and PTS; and (iii) the concept that statins and other anti-inflammatory therapies could reduce VWS and PTS.


Author(s):  
Chase W. Kessinger ◽  
Guanming Qi ◽  
Malek Z.O. Hassan ◽  
Peter K. Henke ◽  
Ahmed Tawakol ◽  
...  

Background: The postthrombotic syndrome is a common, often morbid sequela of venous thrombosis (VT) that arises from thrombus persistence and inflammatory scarring of juxtaposed vein walls and valves. Noninvasive 18 F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) imaging can measure neutrophil inflammation in VT. Here, we hypothesized (1) early fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) VT inflammation can predict subsequent vein wall scarring (VWS) and (2) statin therapy can reduce FDG-PET VT inflammation and subsequent VWS. Methods: C57BL/6J mice (n=75) underwent induction of stasis-induced VT of the inferior vena cava or jugular vein. Inferior vena cava VT mice (n=44) were randomized to daily oral rosuvastatin 5 mg/kg or saline starting at day −1. Subgroups of mice then underwent FDG-PET/CT 2 days after VT induction. On day 14, a subset of mice was euthanized, and VWS was assessed via histology. In vitro studies were further performed on bone marrow-derived neutrophils. Results: Statin therapy reduced early day 2 FDG-PET VT inflammation, thrombus neutrophil influx, and plasma IL (interleukin)-6 levels. At day 14, statin therapy reduced VWS but did not affect day 2 thrombus mass, cholesterol, or white blood counts, nor reduce day 2 glucose transporter 1 or myeloperoxidase expression in thrombus or in isolated neutrophils. In survival studies, the day 2 FDG-PET VT inflammation signal as measured by mean and maximum standardized uptake values predicted the extent of day 14 VWS (area under the receiver operating characteristic curve =0.82) with a strong correlation coefficient ( r ) of r =0.73 and r =0.74, respectively. Mediation analyses revealed that 40% of the statin-induced VWS reduction was mediated by reductions in VT inflammation as quantified by FDG-PET. Conclusions: Early noninvasive FDG-PET/CT imaging of VT inflammation predicts the magnitude of subsequent VWS and may provide a new translatable approach to identify individuals at risk for postthrombotic syndrome and to assess anti-inflammatory postthrombotic syndrome therapies, such as statins.


2021 ◽  
Author(s):  
JooHyun O ◽  
Su Jin Lim ◽  
Hao Wang ◽  
Jeffrey P. Leal ◽  
Hui-Kuo G. Shu ◽  
...  

Abstract Background: The aim of this study was to assess the reader variability in quantitatively assessing pre- and post-treatment 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography/computed tomography ([18F]FDG PET/CT) scans in a defined set of images of cancer patients using the same semi-automated analytical software (Auto-PERCIST™), which identifies tumor peak standard uptake value corrected for lean body mass (SULpeak) to determine [18F]FDG PET quantitative parameters.Methods: Paired pre- and post-treatment [18F]FDG PET/CT images from 30 oncologic patients and Auto-PERCIST™ semi-automated software were distributed to 13 readers across US and international sites. One reader was aware of the relevant medical history of the patients (readreference), whereas the 12 other readers were blinded to history but had access to the correlative images. Auto-PERCIST™ was set up to first automatically identify the liver and compute the threshold for tumor measurability (1.5 x liver mean) + (2 x liver standard deviation [SD]), and then detect all sites with SULpeak greater than the threshold. Next, the readers selected sites they believed to represent tumor lesions. The main performance metric assessed was the percent change in the SULpeak (%ΔSULpeak) of the hottest tumor identified on the baseline and follow up images. Results: The intra-class correlation coefficient (ICC) for the %ΔSULpeak of the hottest tumor was 0.87 (95%CI: [0.78, 0.92]) when all reads were included (n=297). Including only the measurements that selected the same target tumor as the readreference (n=224), the ICC for %ΔSULpeak was 1.00 (95%CI: [1.00, 1.00]). The Krippendorff alpha coefficient for response (complete or partial metabolic response, versus stable or progressive metabolic disease on PET Response Criteria in Solid Tumors 1.0) was 0.91 for all reads (n=380), and 1.00 including for reads with the same target tumor selection (n=270).Conclusion: Quantitative tumor [18F]FDG SULpeak changes measured across multiple global sites and readers utilizing Auto-PERCIST™ show very high correlation. Harmonization of methods to single software, Auto-PERCIST™, resulted in virtually identical extraction of quantitative tumor response data from [18F]FDG PET images when the readers select the same target tumor.


2013 ◽  
Vol 52 (03) ◽  
pp. 101-106 ◽  
Author(s):  
K. Chun ◽  
Y. Hong ◽  
J. Hah ◽  
I. Cho ◽  
E. Kong

Summary Purpose: Kikuchi disease (KD) is a benign and self-limited syndrome characterized by cervical lymphadenopathy. This study evaluated 18F-fluorodeoxyglucose positron emission tomography/ computed tomography (FDG PET/ CT) findings in patients with KD and analyzed their imaging features. Patients, material, methods: We evaluated the FDG PET/CT findings of 22 patients (14 men, 8 women) with KD, ranging in age from 9 to 73 years. All patients had been diagnosed based on the pathological findings of biopsy. We examined the locations, metabolic activity and size of hypermetabolic lymph nodes (LNs) on FDG PET/CT imaging with medical history including laboratory results. Results: Among the 22 patients, we identified 619 hypermetabolic LNs which had maximum standard uptake value (SUVmax) above 3.0. The 16 patients were studied with FDG PET/CT to identify the cause of fever, another 5 patients for their neck masses, and the remaining patient for his left inguinal mass. Hypermetabolic LNs were noted in neck (18 bilaterally, 2 right, 1 left) of 21 patients, axilla of 10, mediastinum of 9, abdomen of 17, pelvis of 6, and inguinal area of 3. The SUVmax of FDG uptake in affected LNs by patient base analysis were 6.2–29.4. Of the 619 hypermetabolic LNs identified, 440 LNs (71.1%) were less than 10 mm in their short axis determined by CT, and were occasionally aggregated. No patient showed solid organ hypermetabolic lesion in FDG PET/CT. Conclusion: Kikuchi disease could present multiple hypermetabolic LNs in body on FDG PET/CT. Based on the physical findings, consideration of the generalized distribution of the relatively small-sized hypermetabolic LNs, FDG PET/CT may be useful as a diagnostic tool in cases of Kikuchi disease.


Diagnostics ◽  
2019 ◽  
Vol 9 (3) ◽  
pp. 92 ◽  
Author(s):  
Larg ◽  
Apostu ◽  
Peștean ◽  
Gabora ◽  
Bădulescu ◽  
...  

Thyroid incidentalomas detected by 18 fluoro-2-deoxy-d-glucose (FDG)-positron emission tomography/computed tomography (PET/CT) are a real challenge for nuclear medicine physicians and clinicians. This study aimed to evaluate the risk of malignancy for patients with focal thyroid incidentalomas (TIs) diagnosed through FDG PET/CT. Data from 6900 patients, with a known primary tumor, who had an FDG PET/CT investigation performed were analyzed for the presence of incidental thyroid uptake. The focal TIs were reported, and the patients were referred for further investigation to the endocrinology department. There were 126 patients (1.82%) who presented with focal thyroid uptake, and for 87 of them, investigations were completed with ultrasonography (US), and for 29 with a fine needle aspiration biopsy (FNAB) procedure. Malignancy was detected in 7.93% (10/126) of cases. An arbitrary cutoff value of four was established for the standard uptake value lean body mass (SUVlbm Max) to differentiate the malignant nodules from the benign ones, and this value was significantly associated with malignancy (p = 0.0168). TIs are not so frequent, but they have a potential malignancy risk, and a proper evaluation is required. Even though SUVlbm Max is a predictive factor for malignancy, the FNAB remains the main diagnostic method for the therapeutic management of these patients.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Joo Hyun O ◽  
◽  
Su Jin Lim ◽  
Hao Wang ◽  
Jeffrey P. Leal ◽  
...  

Abstract Background The aim of this study was to assess the reader variability in quantitatively assessing pre- and post-treatment 2-deoxy-2-[18F]fluoro-d-glucose positron emission tomography/computed tomography ([18F]FDG PET/CT) scans in a defined set of images of cancer patients using the same semi-automated analytical software (Auto-PERCIST™), which identifies tumor peak standard uptake value corrected for lean body mass (SULpeak) to determine [18F]FDG PET quantitative parameters. Methods Paired pre- and post-treatment [18F]FDG PET/CT images from 30 oncologic patients and Auto-PERCIST™ semi-automated software were distributed to 13 readers across US and international sites. One reader was aware of the relevant medical history of the patients (readreference), whereas the 12 other readers were blinded to history but had access to the correlative images. Auto-PERCIST™ was set up to first automatically identify the liver and compute the threshold for tumor measurability (1.5 × liver mean) + (2 × liver standard deviation [SD]) and then detect all sites with SULpeak greater than the threshold. Next, the readers selected sites they believed to represent tumor lesions. The main performance metric assessed was the percent change in the SULpeak (%ΔSULpeak) of the hottest tumor identified on the baseline and follow-up images. Results The intra-class correlation coefficient (ICC) for the %ΔSULpeak of the hottest tumor was 0.87 (95%CI: [0.78, 0.92]) when all reads were included (n = 297). Including only the measurements that selected the same target tumor as the readreference (n = 224), the ICC for %ΔSULpeak was 1.00 (95%CI: [1.00, 1.00]). The Krippendorff alpha coefficient for response (complete or partial metabolic response, versus stable or progressive metabolic disease on PET Response Criteria in Solid Tumors 1.0) was 0.91 for all reads (n = 380) and 1.00 including for reads with the same target tumor selection (n = 270). Conclusion Quantitative tumor [18F]FDG SULpeak changes measured across multiple global sites and readers utilizing Auto-PERCIST™ show very high correlation. Harmonization of methods to single software, Auto-PERCIST™, resulted in virtually identical extraction of quantitative tumor response data from [18F]FDG PET images when the readers select the same target tumor.


2020 ◽  
Author(s):  
JooHyun O ◽  
Su Jin Lim ◽  
Hao Wang ◽  
Jeffrey P. Leal ◽  
Hui-Kuo G. Shu ◽  
...  

Abstract Background: The aim of this study was to assess the reader variability in quantitatively assessing pre- and post-treatment F-18 fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) scans in a defined set of images of cancer patients using the same semi-automated analytical software (Auto-PERCIST™), which identifies tumor peak standard uptake value corrected for lean body mass (SULpeak) to determine 18F-FDG PET quantitative parameters.Methods: Paired pre- and post-treatment FDG PET/CT images from 30 oncologic patients and Auto-PERCIST™ semi-automated software were distributed to 13 readers across US and international sites. One reader was aware of the relevant medical history of the patients (readreference), whereas the 12 other readers were blinded to history but had access to the correlative images. Auto-PERCIST™ was set up to first automatically identify the liver and compute the threshold for tumor measurability (1.5 x liver mean) + (2 x liver standard deviation [SD]), and then detect all sites with SULpeak greater than the threshold. Next, the readers selected sites they believed to represent tumor lesions. The main performance metric assessed was the percent change in the SULpeak (%ΔSULpeak) of the hottest tumor identified on the baseline and follow up images. Results: The intra-class correlation coefficient (ICC) for the %ΔSULpeak of the hottest tumor was 0.87 (95%CI: [0.78, 0.92]) when all reads were included (n=297). Including only the measurements that selected the same target tumor as the readreference (n=224), the ICC for %ΔSULpeak was 1.00 (95%CI: [1.00, 1.00]). The Krippendorff alpha coefficient for response (complete or partial metabolic response, versus stable or progressive metabolic disease on PET Response Criteria in Solid Tumors 1.0) was 0.91 for all reads (n=380), and 1.00 including for reads with the same target tumor selection (n=270).Conclusion: Quantitative tumor FDG SULpeak changes measured across multiple global sites and readers utilizing Auto-PERCIST™ show very high correlation. Harmonization of methods to single software, Auto-PERCIST™, resulted in virtually identical extraction of quantitative tumor response data from FDG PET images when the readers select the same target tumor.


2020 ◽  
pp. 028418512096671
Author(s):  
Noriaki Tomura ◽  
Toshiyuki Saginoya ◽  
Hiromi Goto

Background Positron emission tomography (PET) findings for gliomatosis and lymphomatosis have been rarely reported. Purpose To compare PET/computed tomography (CT) findings using 11C-methionine (MET) from PET/CT findings using 18F-fluorodeoxy glucose (FDG) for patients with lymphomatosis or gliomatosis of the brain. Material and Methods Participants comprised all 10 patients with lymphomatosis or gliomatosis of the brain treated at our institution in the past 12 years. Underlying pathologies comprised intravascular lymphoma (n = 1), lymphomatosis (n = 3), and gliomatosis (n = 6). All cases were pathologically diagnosed. In seven patients, both MET-PET/CT and FDG-PET/CT were performed simultaneously in a single study. In three patients, only FDG-PET/CT was performed. The degree of tracer accumulation to the lesion was evaluated qualitatively. Quantitatively, the ratio of maximum standard uptake value (SUVmax) in tumor to that in normal tissue (T/N ratio) was measured and compared between FDG and MET. Results Qualitatively, MET accumulated to part of the lesion in six of seven patients and almost all of the lesion in one in seven patients. FDG accumulated to part of the lesion in three of ten patients and almost all of the lesion in one of ten patients. No FDG accumulation was seen in the lesion in six patients. Quantitatively, mean ± SD T/N ratio was significantly higher with MET (2.11 ± 0.63) than with FDG (1.18 ± 0.84; P < 0.05, Wilcoxon signed-rank test). Conclusion In lymphomatosis and gliomatosis, FDG accumulates in only part of the lesion. FDG is thus less suitable than MET for depicting these lesions.


Author(s):  
Christian Reeps ◽  
Michael W. Gee ◽  
Wolfgang A. Wall ◽  
Hanns-Henning Eckstein

The widely accepted hypothesis that mechanobiological transduction plays a central role in pathogenesis of abdominal aortic aneurysm (AAA) is plausible, but so far was never directly proven in vivo for methodical reasons. At present, stresses and strains acting in AAA wall can be assessed by computational finite element analyses (FEA) [1,2,3]. Independently, it has also been reported that glycolytic activity in AAA wall non-invasively assessed by [18F]flourodeoxyglucose positron emission tomography/CT (FDG-PET/CT) is associated with increased proteolytic activity, structure-protein-degradation, AAA progression and consequently AAA wall instability as well as rupture risk [4]. Both methods were studied by our research group in an individual AAA patient [5]. Here, the correlation of computational biomechanics with metabolic activity assessed by FDG-PET/CT is analyzed in a larger patient cohort (n=18) [8].


Author(s):  
Marco Tana ◽  
Silvio di Carlo ◽  
Marcello Romano ◽  
Massimo Alessandri ◽  
Cosima Schiavone ◽  
...  

Background:18F-fluorodeoxyglucose positron emission tomography integrated with computed tomography (18-F-FDG-PET/CT) is getting wide consensus in the diagnosis and staging of neoplastic disorders and represents a useful tool in the assessment of various inflammatory conditions. </P><P> Discussion: Sarcoidosis is an uncommon disease characterized by the systemic formation of noncaseating granulomas. Lungs are the sites most often affected, and investigation with high resolution computed tomography and biopsy is essential to achieve a correct diagnosis. 18-F-FDGPET/ CT is effective in the assessment of pulmonary sarcoidosis by demonstrating pulmonary and extrathoracic involvement and findings correlate well with pulmonary function in patients affected.Conclusion:This review would illustrate the usefulness and limits of 18-F-FDG-PET/CT in the assessment of pulmonary sarcoidosis.


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