The Metabolic Activity of the Spleen and Bone Marrow in...

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The Metabolic Activity of the Spleen and Bone Marrow in Patients with Acute

Myocardial Infarction Evaluated by 18F-FDG PET Imaging

Kim et al.: Activation of the spleen and bone marrow in AMI

Eung Ju Kim, MD, PhD;1 Sungeun Kim, MD, PhD;2

Hong Seog Seo, MD, PhD;1 Dong Oh Kang, MD1

1Cardiovascular Center, Division of Cardiology, Department of Internal Medicine;

2Nuclear Medicine, Korea University Guro Hospital, Korea University College of Medicine,

Seoul, Korea

Correspondence to Hong Seog Seo, MD, PhD Division of Cardiology, Department of Internal Medicine, Korea University Guro Hospital, Korea University College of Medicine, 80 Guro-dong, Guro-gu, Seoul 152-703, Korea Tel: 82-2-2626-3018, Fax: 82-2-863-1109 Email: [email protected]

DOI: 10.1161/CIRCIMAGING.113.001093

Journal Subject Codes: [4] Etiology: acute myocardial infarction; [32] Diagnostic testing:

nuclear cardiology and PET; [134] Atherosclerosis: pathophysiology

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Abstract

Background—Atherosclerosis is considered to be an inflammatory disease associated with the

activation of hematopoietic and immune-related organs such as the bone marrow (BM) and

spleen. We evaluated the metabolic activity of those organs and of the carotid artery with 18F-

FDG PET in patients with coronary artery disease, including acute myocardial infarction (AMI).

Methods and Results—Whole-body combined 18F-FDG PET/CT was performed in 32 patients

with AMI, 33 patients with chronic stable angina, and 25 control subjects. The mean standard

uptake value (SUV) was calculated in the regions of interest in the spleen and the BM of lumbar

vertebrae. The target-to-background ratio (TBR) of the SUVs of the carotid artery and jugular

vein was also calculated. In patients with AMI, the SUVs of the BM (1.67±0.16) and spleen

(2.57±0.39), as well as the TBR of the carotid artery (2.13±0.42), were significantly higher than

the corresponding values of patients with angina (1.22±0.62; 2.03±0.35; 1.36±0.37, all p<0.001)

and controls (0.80±0.44; 1.54±0.26; 1.22±0.22, all p<0.001) independent of traditional

cardiovascular risk factors and high-sensitivity CRP (hsCRP). In all groups combined, the TBR

of the carotid artery was significantly associated with the SUVs of the BM (r=0.535, p<0.001),

spleen (r=0.663, p<0.001), and hsCRP (r=0.465, p<0.001).

Conclusions—The metabolic activity of the BM and spleen as well as of the carotid artery was

highest in patients with AMI, intermediate in patients with angina, and lowest in control subjects.

The activation of the BM and spleen was significantly associated with inflammatory activity of

the carotid artery.

Keywords: spleen, bone marrow, coronary artery disease, positron emission tomography

Basic biological and clinical research supports the role of inflammation in the initiation, growth,

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and rupture of atherosclerotic plaques.1 At every stage of atherosclerosis, monocyte-derived

macrophages are the principal mediators of inflammation.2, 3 Recent studies lend some clarity to

the role of inflammation in driving the atherogenic response to hypercholesterolemia and suggest

that this process is initiated in the bone marrow (BM) and spleen.4-6 In response to

hypercholesterolemia, both the BM and spleen overproduce inflammatory monocytes that enter

the circulation, accumulate in lesions, and differentiate into macrophages.7

Acute myocardial ischemic injury8 and infarction (AMI)9 activate the sympathetic

nervous system and trigger a cascade of hematopoietic stem and progenitor cell (HSPC)

proliferation in the BM and emigration to the spleen, as well as peripheral monocytosis.7 In this

process, the spleen acts as an extramedullary hematopoietic reservoir producing inflammatory

monocytes that aggravate atherosclerosis.8 Thus, this inflammatory linkage between the BM,

spleen and blood following an acute cardiac event may intensify the chronic inflammatory

process involved in atherosclerosis, independently from the primary myocardial wound site.7

This mechanism of systemic inflammation in atherosclerotic disease initiated by the BM and

spleen has been studied in animal models, but not in humans with coronary artery disease (CAD).

Activated inflammatory cells express high levels of glucose transporters and accumulate

18F-fluorodeoxyglucose (18F-FDG).10, 11 For this reason, 18F-FDG positron emission tomography

(PET) is a useful noninvasive imaging technique to evaluate the inflammatory status of

atherosclerotic plaques12_ENREF_11 and periodontal disease.13_ENREF_16 Theoretically, the

metabolic activity of the BM and spleen can be also evaluated by PET using 18F-FDG.10, 11

This study has 3 objectives: (1) to determine whether the metabolic activation of the BM

and spleen is associated with AMI; (2) whether the degree of metabolic activation of these

organs is associated with inflammatory activity at carotid plaques remote from the coronary

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arteries, and (3) whether the activity in the BM and spleen is higher in patients with chronic

stable angina (CSA) than in control subjects. We measured 18F-FDG uptake in the spleen, BM,

and carotid artery using whole-body 18F-FDG-PET/computed tomography (CT) in patients with

AMI, CSA, and control subjects without a history of CAD.

Methods

Study Subjects

Between June 2008 and March 2009, we prospectively recruited patients at Korea University

Guro Hospital who were diagnosed with AMI or CSA. AMI was defined as typical changes in

biochemical markers of myocardial necrosis along with at least 1 of the following: ischemic

symptoms, electrocardiographic changes indicative of new ischemia, development of pathologic

Q waves, or imaging evidence of new loss of viable myocardium or new regional wall motion

abnormalities.14 CSA was defined as the presence of stable anginal symptoms for at least 6

months with at least 50% luminal narrowing in at least 1 major coronary artery on angiography.

Criteria for exclusion from the control group were a history of cardiovascular disease

(myocardial infarction, unstable angina, stroke, or cardiovascular revascularization), greater than

stage 1 hypertension (resting blood pressure 160/100 mmHg), uncontrolled diabetes mellitus

(glycated hemoglobin >9%), malignancy, or severe renal or hepatic disease. Subjects with a

history of an inflammatory condition, or those taking inflammation-modulating medications

within the prior 6 months, were excluded from the study. All participants provided written

informed consent and the Korea University Institutional Review Board approved this study

protocol.

The following clinical and demographic parameters were recorded: age, sex, body mass

index, waist circumference, the presence of hypertension (defined as those taking

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antihypertensive medications or 2 blood pressure recordings over 140/90 mmHg), the presence

of diabetes mellitus (defined as those undergoing treatment with diet and/or medications or a

fasting serum glucose >126 mg/dl), and dyslipidemia (defined as those taking lipid-lowering

medications or a fasting serum total cholesterol 240 mg/dl, triglycerides 200 mg/dl, high

density lipoprotein cholesterol <40 mg/dl, or low density lipoprotein cholesterol 160 mg/dl).

Cardiac troponin T and creatine kinase-MB fraction (CK-MB) were measured using

electrochemiluminescence immunoassays on the Elecsys 2010 analyzer (Roche Diagnostics,

Indianapolis, Inidiana, USA). Concentrations of troponin T >0.1 ng/mL and CK-MB >6.73

ng/mL in men or >3.77 ng/mL in women were used as cutoff values to diagnose AMI based on

the manufacturer’s instructions.

18F-FDG- PET/CT Imaging

18F-PET/CT was performed using the Gemini TF 16-Slice PET/CT scanner (Philips Medical

Systems, Cleveland, Ohio, USA). Patients diagnosed with AMI, all of whom were successfully

treated by primary percutaneous coronary intervention, underwent PET/CT within 10 days of the

event when they were clinically stable (mean: 6.3 days; range: 1-10). The TF scanner is a new

high-performance, time-of-flight-capable, fully 3-dimensional PET scanner that uses lutetium-

yttrium oxyorthosilicate crystals.15 After at least 12 hours of fasting, FDG (5.19 MBq/kg) was

injected intravenously, after which patients rested in a quiet room for 60 minutes. In diabetic

patients, who may have a different blood clearance from nondiabetic patients, we determined

blood glucose level before 18F-FDG administration and changed the PET schedule if it exceeded

180 mg/dl to reduce the metabolic effect on FDG uptake. Whole-body PET images (from below

the cerebellum to the inguinal region) were acquired for 10 minutes (1 minute per bed position).

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Analysis of Positron Emission Tomography Images

PET images were analyzed on a dedicated workstation (Extended Brilliance Workspace 3.5;

Philips). Right carotid FDG uptake was measured along the length of the right carotid vessel,

starting at the bifurcation and extending inferiorly and superiorly every 4 mm for a total of 8

consecutive PET/CT images for each subject. Arterial FDG uptake was quantified in the region

of interest (ROI) around each artery on every slice of the co-registered transaxial fusion PET/CT

images. The highest standard uptake values (SUVs) of the ROIs of all 8 slices within the right

carotid artery were averaged together for each subject. Next, the arterial SUV was divided by the

blood-pool SUV measured from the jugular vein for normalization. In this way, the arterial

target-to-background ratio (TBR) was calculated for each subject. 18F-FDG uptake was measured

in the spleen by placing an ROI around the organ on all transaxial slices. The highest SUVs from

all transaxial slices were recorded and their average was used as the mean SUV for the entire

organ. BM 18F-FDG uptake was calculated under CT-guided anatomical reference from the third

to fifth lumbar vertebrae,16 and the average of the highest SUVs was used as the mean SUV for

analysis. To determine the variability of the mean SUV measurements, images from 20 subjects

were analyzed twice, several weeks apart, by 2 readers who were unaware of the subjects’

clinical histories. The intra- and inter-observer correlation coefficient values of the mean SUV

measurements were greater than 0.9.

Statistical Analysis

Baseline characteristics of the participants were analyzed according to the 3 main study groups.

Frequencies and proportions were reported for categorical variables, and either mean ± standard

deviation or median with interquartile range were reported for continuous variables based on

normality of distribution. The Pearson chi-squared test, Fisher’s exact test, one-way analysis of

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variance (ANOVA), and the Kruskal-Wallis test were used to compare variables between groups.

Subsequent comparisons were performed by Bonferroni’s post-hoc test, or the Mann-Whitney U-

test or Fisher’s exact test with Bonferroni corrected p values. The SUVs of the BM and spleen

and the TBRs of the carotid artery were compared between the 3 groups using analysis of

covariance (ANCOVA) with Bonferroni multiple comparisons, in which the possible

confounding effects of sex, waist circumference, hypertension, diabetes, dyslipidemia, smoking,

statin use, and high-sensitivity C-reactive protein (hsCRP) were taken into account by including

them in the model as covariates. Spearman correlation analysis was performed to identify the

relationship between 18F-FDG uptake in multiple organs and hsCRP. Multiple linear regression

analyses using the TBR of the carotid artery as a dependent variable were also performed to

investigate whether there was an independent relationship between 18F-FDG uptake in each

organ and uptake in the carotid artery. Data were analyzed using SPSS for Windows version 20.0

(SPSS, Chicago, IL, USA). P-values less than 0.05 were considered statistically significant.

Results

Clinical and laboratory characteristics

The subjects included 51 men (56.7%) and 39 women (43.3%). Women comprised the majority

of the control group, while men comprised the majority of the CSA and AMI groups. The mean

age of subjects was 57.7±10.1 years, and did not differ significantly between groups. Compared

to the control group, most of the traditional cardiovascular risk factors, such as hypertension,

diabetes, dyslipidemia, and smoking, were more prevalent in the CSA and AMI groups. The

prevalence of those risk factors was not significantly different between the CAD groups.

Subjects taking statins comprised nearly a third of total subjects in both CAD groups upon initial

presentation. There were significant stepwise increases in white blood cell count and hsCRP

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from the control group to the AMI group (Table 1).

Comparison of FDG uptake in the bone marrow, spleen, and carotid artery between groups

The mean maximum SUV levels in the spleen and BM were incrementally and significantly

higher in the AMI and CSA groups compared to the control group (Table 1, Figure 1A, Figure

2A, and Figure 2B). The AMI group had higher carotid artery TBRs than did the CSA and

control groups (Table 1, Figure 1B, and Figure 2C). Although the carotid artery TBR of the CSA

and control groups did not differ significantly (Table 1 and Figure 2C), it reached statistical

significance after adjusting for sex, waist circumference, hypertension, diabetes, dyslipidemia,

smoking, statin use, and hsCRP in ANCOVA analysis (for the carotid artery TBR, AMI vs. CSA

group, p<0.001; CSA vs. control group, p=0.038). The SUVs of the spleen and BM were also

significantly different between groups after the same adjustments (for spleen SUV, AMI vs. CSA

group, p<0.001; CSA vs. control group, p<0.001, for BM SUV, AMI vs. CSA group, p=0.003;

CSA vs. control group, p=0.017).

Correlation between high-sensitivity C-reactive protein and FDG uptake in the bone marrow,

spleen, and carotid artery

The TBR of the carotid artery and SUVs of the BM and spleen correlated significantly with each

other in study subjects overall. Without adjustment, the TBR of the carotid artery was most

highly correlated with the SUV of the spleen. HsCRP was also significantly correlated with FDG

uptake in the BM, spleen, and carotid artery (Table 2). In the AMI group, there was no

correlation between peak serum CK-MB and troponin-T levels and FDG uptake in the BM,

spleen, or carotid artery (data not shown).

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Relationship between carotid artery target-to-background ratio and bone marrow FDG uptake,

spleen FDG uptake, and high-sensitivity C-reactive protein

Multiple linear regression analysis of the overall study population, which included age, sex,

waist circumference, hypertension, diabetes, dyslipidemia, smoking, and statin use as covariates,

revealed an independent relationship between carotid artery TBR, the SUVs of the spleen and

BM, and hsCRP. The SUVs of the spleen and BM were significantly associated with carotid

artery TBR even after further adjustment for hsCRP. In contrast, hsCRP did not maintain a

significant association with carotid artery TBR when the SUV of the BM or spleen was entered

into the model as an independent variable (Table 3).

Discussion

This study revealed significant associations between CAD, the metabolic activity of the spleen

and BM, and the inflammatory activity of the carotid artery independent of traditional

cardiovascular risk factors and hsCRP level. Those activities were highest in patients with AMI,

intermediate in patients with CSA, and lowest in the control group. The 18F-FDG uptake in the

carotid artery was significantly associated with the metabolic activity of the spleen and BM as

well as with hsCRP level.

Most studies that support the association between inflammation and CAD have been

based on epidemiologic analysis of circulating biomarkers17-19 and animal experiments.20-23

Recent studies have identified that the role of the spleen and BM in chronic and acute

inflammation in atherosclerotic disease. In chronic inflammation of atherosclerosis, both the BM

and spleen are involved. HSPCs progressively relocate from the BM to the splenic red pulp,

where they clonally expand with granulocyte macrophage colony-stimulating factor and

interleukin-3 and differentiate into inflammatory monocytes.5 Monocytes born in the spleen

BM or sppppppleen wwasasasasasasas e

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intravasate, circulate, and accumulate into atherosclerotic lesions in murine models.5_ENREF_24

Our findings are consistent with this knowledge, in that significantly higher activity was found in

the BM, spleen, and carotid artery in the CSA group than in the control group.

Using 18F-FDG PET, Assmus et al. found significantly higher metabolic activity in the

BM and significantly larger populations of hematopoietic CD34+ and CD133+ cells in BM

aspirates from patients within 7 days after AMI than in patients with chronic post-ischemic heart

failure.24 The same authors reported that AMI induced by ligating a coronary artery or

application of other stressors can activate stem cells in the BM in non-atherosclerotic mice.24 It

has also been reported that acute ischemic myocardial injury triggers emergency hematopoiesis

in the BM and spleen,7 and that AMI liberates HSPCs from BM niches via signals from the

sympathetic nervous system.9_ENREF_25 The progenitors then seed the spleen and yield a

sustained boost in monocyte production to meet demand in the infarcted myocardium.7, 9 This

process, however, may have unintended consequences, such as acceleration of underlying

atherosclerosis triggering reinfarction or stroke.7, 9 Dutta et al. found that in ApoE-/- mice, AMI

accelerates underlying aortic atherosclerosis.9

In light of these findings, our AMI group indeed demonstrated higher metabolic activity

in the spleen and BM than the CSA group. The greater inflammatory activity in the carotid

arteries of the AMI group compared to the CSA group may be evidence of this damaging

accumulation of monocytes in atherosclerotic lesions. Moreover, we found that the metabolic

activity of the carotid artery was closely associated with that of the spleen and BM as well as

with the level of hsCRP in the overall patient population. These findings suggest that the

inflammatory status of atherosclerosis is influenced by systemic inflammation modulated by the

spleen and BM.

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Metabolic activation of the major organs that harbor inflammatory cells such as the

spleen,8 or that participate in inflammatory cell production, such as the BM and spleen,5, 9 has

been revealed using 18F-FDG-PET in a variety of systemic conditions, including infection,25

cancer,16 connective tissue diseases26 and systemic autoimmune disorders.27 However, few

studies have demonstrated the metabolic activation of the BM and spleen in humans with CAD.

To the best of our knowledge, this is the first in vivo human study showing the metabolic activity

of the spleen and BM in patients with CAD using a molecular imaging tool.

In our study, the metabolic activity of the spleen and BM was high in patients with AMI

even after a mean of 6.3 days from the event. Inflammatory monocytes, which have been found

to be chronically expanded in the blood pool of atherosclerotic apoE-/- mice, impair infarct

healing through prolonged presence in the infarct and deregulated resolution of inflammation.28

This result suggests that patients with AMI who have underlying inflammation associated with

atherosclerosis may have prolonged activation of the organs involved in inflammation. Further

studies are needed to determine the time period during which activation of the spleen and BM

persists after AMI in humans.

Our study has several limitations. First, its cross-sectional design, small sample size, and

significant differences between subjects and controls may have introduced various levels of bias.

Although we attempted to adjust for these differences and the small sample size, our model may

not be sufficiently powered to support the results. Second, we did not perform coronary

angiography in the control group to confirm the presence of coronary atherosclerosis and this

may have affected our results. Third, we did not perform histopathological analysis of tissue

samples from the spleen or BM. However, it is already known that 18F-FDG accumulates in

tissue macrophages and its intensity correlates with the staining density of tissue macrophages in

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corresponding histological sections of specimens.10, 11 Fourth, the patients with AMI may have

had elevated levels of catecholamines and endogenous steroids associated with stress in addition

to their underlying inflammatory state. However, we were not able to control for all factors

affecting glucose metabolism and FDG uptake, including levels of insulin, catecholamines,

steroids, and other substrates in plasma, which may have affected our results. Fifth, we did not

control for other factors affecting systemic inflammation, such as life style habits, low-grade

chronic infections, and genetic predisposition. Finally, we did not measure the biomarkers of

HSPC in the BM or monocyte subsets in the peripheral blood. In short, this study was not

designed to definitively prove an etiological hypothesis, but was an observational study designed

to measure metabolic activity of the spleen and BM in patients with CAD as an indirect probe

into a previously established condition.

In conclusion, the metabolic activity of the BM and spleen as well as of the carotid artery

was highest in patients with AMI, intermediate in patients with CSA, and lowest in controls. The

relationship between those parameters and CAD status was independent of traditional

cardiovascular risk factors. Activation of the BM and spleen was closely associated with the

activity in the carotid artery. Our results offer insights into risk stratification, monitoring of

therapy, and physiological changes in the early stages of atherosclerosis, when intervention may

be most effective.

Sources of Funding

This study was partly supported by the Korea Institute of Science and Technology Institutional

Program (Project No. 2E24080); a grant from the Korean Health Technology R&D Project of the

Ministry for Health, Welfare & Family Affairs of the Republic of Korea (A070001); and a grant

from the Korea University-Korea Institute of Science and Technology (KU-KIST) Graduate

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School Converging Science and Technology(R1106223).

Disclosures

None.

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28. Panizzi P, Swirski FK, Figueiredo JL, Waterman P, Sosnovik DE, Aikawa E, Libby P,

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Pittet M, Weissleder R, Nahrendorf M. Impaired infarct healing in atherosclerotic mice with ly-6c(hi) monocytosis. J Am Coll Cardiol. 2010; 55:1629-1638

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Table 1. Baseline characteristics of study subjects. AMI (n=32) CSA (n=33) Control (n = 25) p-value

Age, yrs 56.9±11.6a 61.2±11.5a 57.1±7.5a 0.206

Men 21 (65.6)a 24 (72.7)a 6 (24.0) <0.001

BMI (kg/m2) 24.6±2.6a,b 26.0±4.0b 23.5±2.9a 0.022 WC (cm) 83.4±16.3 92.3±11.4 80.9±7.5 <0.001 Hypertension 15 (46.9)a 19 (57.6)a 1 (4.0) <0.001

Diabetes 13 (40.6)a 13 (39.4) a 2 (8.0) 0.013

Dyslipidemia 19 (59.4)a 16 (48.5)a 2 (8.0) <0.001

Smoking 13 (40.6)a 13 (39.4)a 2 (8.0) 0.013

Statin use 9 (28.1)a 11 (33.3)a 0 (0) 0.006

Total cholesterol, mg/dL 187±44 a 156±35 189±25 a 0.001

Triglycerides, mg/dL 137±142 a, b 160±100 a 87±44 b 0.009

88 (58-168) 113 (85-254) 68 (56-122)

HDL-cholesterol, mg/dL 45±12 a 49±15 a 59±16 0.001

LDL-cholesterol, mg/dL 124±42 a 92±30 115±24 a 0.001

HbA1c, % 6.9±2.1a 7.0±1.6a 5.7±0.4 0.001

6.1 (5.7-7.8) 6.6 (5.7-7.5) 5.6 (5.4-5.9)

WBC, x103/uL 10.9±3.3 6.5±1.2 5.0±1.3 <0.001

10.6 (8.4-12.6) 6.5 (5.5-7.7) 5.0 (3.9-6.3) hsCRP, mg/L 3.48±3.10 1.53±1.55 0.55±0.57 <0.001 1.88 (1.05-5.97) 1.16 (0.32-2.49) 0.41 (0.17-0.82) peak CK-MB, ng/mL 145.6±127.3 - - - peak troponin-T, ng/mL 3.66±4.64 - - -

TBR

Carotid artery 2.13±0.42 1.36±0.37a 1.16±0.09a <0.001

SUV Spleen 2.57±0.39 2.03±0.35 1.54±0.26 <0.001 Bone marrow 1.67±0.16 1.22±0.62 0.80±0.44 <0.001

Data are expressed as mean ± SD; median with interquartile range in parenthesis; or number with percentage in parentheses. P-values represent overall differences across groups as determined by ANOVA or the Kruskal-Wallis test for continuous variables and Pearson’s chi-squared test or Fisher’s exact test for categorical variables. a,b The same letters indicate no statistical significance based on Bonferroni’s post-hoc test, or the Mann-Whitney U-test and, or separate Pearson’s chi-squared test or Fisher’s exact test with Bonferroni corrected p values. AMI, acute myocardial infarction; BMI, body mass index; CSA, chronic stable angina; HDL, high density lipoprotein; hsCRP, high sensitivity C-reactive protein; LDL, low density lipoprotein; SUV, standard uptake value; TBR, target-to-background ratio; WBC, white blood cell; WC, waist circumference.

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Table 2. Spearman correlation analysis between hsCRP level and FDG uptake in the carotid artery, spleen, and BM in the overall study population.

SUV of BM SUV of Spleen hsCRP

TBR of Carotid artery 0.535* 0.663* 0.465*SUV of BM - 0.637* 0.525*SUV of Spleen 0.637* - 0.458*

* p<0.001 BM, bone marrow; hsCRP, high sensitivity C-reactive protein; SUV, standard uptake value; TBR, target-to-background ratio.



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Table 3. Multiple linear regression analysis using the carotid artery TBR as a dependent variable.

p R2 R2adjusted

SUV, bone marrow* 0.438 <0.001 0.329 0.245

SUV, bone marrow † 0.395 <0.001 0.378 0.288

SUV, spleen* 0.688 <0.001 0.461 0.394

SUV, spleen † 0.644 <0.001 0.486 0.412

hsCRP* 0.011 0.040 0.192 0.088 *The association with the carotid artery TBR after adjustment for age, sex, waist circumference, hypertension, diabetes, dyslipidemia, smoking, and statin use. †The association with the carotid artery TBR after adjustment for the above covariates and hsCRP. R2

adjusted = 1 – (1- R2)(N-1)/(N-P-1), where R2= sample R-square, p=number of predictors, N=total sample size.

hsCRP, high sensitivity C-reactive protein; SUV, standard uptake value; TBR, target-to-background ratio.

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Figure Legends

Figure 1. A. Representative examples of maximum-intensity-projection 18F-FDG PET images

showing highly increased uptake and moderately increased uptake throughout the bone marrow

and spleen in patients with acute myocardial infarction (AMI) and chronic stable angina (CSA),

respectively. B. Axial fusion images at the carotid artery level from the same scan showing

diffuse intense uptake of 18F-FDG in the carotid arteries of patients with AMI (arrow) and

moderate uptake in patients with CSA.

Figure 2. Mean differences in spleen SUV (A), BM SUV (B), and the carotid artery TBR (C)

between the 3 study groups. Error bars show 95% confidence intervals of means.

AMI, acute myocardial infarction; BM, bone marrow; CSA, chronic stable angina; SUV,

standard uptake value; TBR, target-to-background ratio.

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Eung Ju Kim, Sungeun Kim, Hong Seog Seo and Dong Oh KangF-FDG PET Imaging18Infarction Evaluated by

The Metabolic Activity of the Spleen and Bone Marrow in Patients with Acute Myocardial

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