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. Author manuscript; available in PMC: 2013 Sep 23.
Published in final edited form as: Int J Obes (Lond). 2009 Jan 13;33(2):226–232. doi: 10.1038/ijo.2008.267

Novel measurements of periaortic adipose tissue in comparison to anthropometric measures of obesity, and abdominal adipose tissue

Christopher L Schlett 4, Joseph M Massaro 3, Sam J Lehman 4, Fabian Bamberg 4, Christopher J O’Donnell 1,5, Caroline S Fox 1,2,*, Udo Hoffmann 4,*
PMCID: PMC3779879  NIHMSID: NIHMS457152  PMID: 19139753

Abstract

Background

Perivascular adipose tissue may be associated with the amount of local atherosclerosis. We developed a novel and reproducible method to standardize volumetric quantification of periaortic adipose tissue by computed tomography (CT) and determined the association with anthropometric measures of obesity, and abdominal adipose tissue.

Methods

Measurements of adipose tissue were performed in a random subset of participants from the Framingham Heart Study (n=100) who underwent multidetector CT of the thorax (ECG triggering, 2.5 mm slice thickness) and the abdomen (helical CT acquisition, 2.5 mm slice thickness). Abdominal periaortic adipose tissue (AAT) was defined by a 5 mm cylindrical region of interest around the aortic wall; thoracic periaortic adipose tissue (TAT) was defined by anatomic landmarks. TAT and AAT were defined as any voxel between −195 HU to −45HU and volumes were measured using dedicated semiautomatic software. Measurement reproducibility and association with anthropometric measures of obesity, and abdominal adipose tissue were determined.

Results

The intra- and inter-observer reproducibility for both AAT and TAT was excellent (ICC: 0.97, 0.97; 0.99, and 0.98, respectively). Similarly, the relative intra-and inter-observer difference was small for both AAT (−1.85±1.28% and 7.85±6.08%; respectively) and TAT (3.56±0.83% and −4.56±0.85%, respectively). Both AAT and TAT were highly correlated with visceral abdominal fat (r=0.65 and 0.77, p<0.0001 for both) and moderately correlated with subcutaneous abdominal fat (r=0.39 and 0.42, p<0.0001 and p=0.009), waist circumference (r=0.49 and 0.57, p<0.0001 for both), and body mass index (r=0.47 and 0.58, p<0.0001 for both).

Conclusion

Standardized semiautomatic CT-based volumetric quantification of periaortic adipose tissue is feasible and highly reproducible. Further investigation is warranted regarding associations of periaortic adipose tissue with other body fat deposits, cardiovascular risk factors, and clinical outcomes.

Keywords: Adipose Tissue, Intra-Abdominal Fat, Tomography, Spiral Computed, Framingham Heart Study, Metabolic Risk Factors

Introduction

Obesity is common, affecting nearly one-third of the US adult population. Obesity is related to multiple co-morbidities including atherosclerotic cardiovascular disease (CVD) (1). Traditional assessment of obesity is limited to anthropometric measurements such as body-mass-index (BMI) or waist circumference (WC) (2), which are robust predictors of obesity related morbidity (3–7).

Recent advances in imaging technology have enabled a direct quantitative assessment of local fat depots such as abdominal visceral and subcutaneous adipose tissue (VAT, SAT, respectively) by dual energy X-ray absorptiometry (DXA) (8), magnetic resonance imaging (MRI) (9, 10), ultrasound (11), or multi-detector computed tomography (MDCT) (12, 13). Initial studies suggest an association between the amount of local adipose tissue (i.e. pericardial fat) and metabolic activity and secretion of endocrine substances, like inflammatory markers (14, 15). Moreover, recent studies suggest the amount of local pericardial adipose tissue is associated with the presence of coronary artery calcification (14, 16, 17). These observations are supported by findings showing that pericardial fat, but not visceral abdominal fat, is associated with the presence of coronary artery calcification (17, 18). Whether adipose tissue surrounding the aorta has a similar association with local aortic calcification is unknown.

Therefore, the goal of this study was to develop standard protocols for volumetric quantification of abdominal and thoracic periaortic adipose tissue in non-contrast enhanced MDCT exams in a community-based sample. We further sought to determine the intra- and inter-observer reproducibility of these new measurements and their association with anthropometric measurements of obesity, and abdominal fat depots.

Methods

Participants for the current study were drawn from the Framingham Heart Study Offspring Cohort who underwent MDCT scanning during the time period June 2002 to March 2005 (n=1422); details regarding recruitment have been detailed elsewhere (19, 20). The present study sample represents a random subset of 100 participants (age range: 37–83 years, 49% women) which was taken to ensure approximately equal number of men and women, and an approximately equal number of participants in each of the age groups of 35–44, 45–54, 55–64, 65–74 and 75–84 years, were represented (approximately 10 per age group per sex). The institutional review boards of the Boston University Medical Center and Massachusetts General Hospital approved the study. All subjects provided written consent.

Multi-detector computed tomography (MDCT) scan protocol

All subjects underwent computed tomography (CT) scanning in a supine position using an eight-slice MDCT (LightSpeed Ultra, General Electric, Milwaukee, WI, USA).

Helical non- gated CT imaging of the abdomen was performed subsequently (tube voltage: 120 kVp, tube current: 320 mA or 400 mA in participants <220 lbs or >220 lbs; respectively). Gantry rotation time was 500 ms with a pitch of 1.33 to cover 150 mm above the upper edge of S1. Slices were obtained with 8 × 2.5 mm detector width and reconstructed with a 2.5 mm slice thickness and a 35 cm field of view. CT imaging of the thorax was performed during a single inspiratory breath hold with a tube voltage of 120 kVp and a tube current of 320 mA in participants with a weight <220 lbs. The tube current was adjusted in participants with a weight >220 lbs to 400 mAs. The scans were acquired using prospective ECG-triggering with the center of the acquisition at 70% with a gantry rotation time of 500 ms and a temporal resolution of 330 ms. The scan covered the region from carina to diaphragm with a slice thickness of 2.5 mm. An average scan length of average of 18 seconds followed from these parameters. The images were reconstructed with 2.5 mm thick, non overlapping slices in 25 cm field of view.

MDCT data analysis

Two experienced observers performed an analysis of all data sets in random order to assess for inter-observer variability (SL and CS), blinded to the readings of the other observer. One reader repeated the analysis 1 week later to assess for intra-observer variability (CS).

Quantitative measurements of perivascular adipose tissue

We measured perivascular adipose tissue volume around the abdominal and thoracic aorta using a dedicated offline workstation (Aquarius 3D Workstation, TeraRecon Inc., San Mateo, CA, USA). Because the CT attenuation in absolute Hounsfield units (HU) corresponds to tissue properties, we applied an automatic threshold based algorithm to identify voxels containing adipose tissue and to determine the volume of adipose tissue using a HU range from −195 to −45 HU (14, 21, 22).

Measurements of Abdominal Periaortic adipose tissue (AAT)

In order to separate periaortic from retroperitoneal adipose tissue and to standardize our measurements, we defined our region of interest in each slice as a circle that had a diameter which was 10 mm larger than the anterior-posterior aortic diameter. This predefined ROI was centered over the aorta (Figure 1). This standardization enabled the capture of a cylinder of periaortic adipose tissue. The volume of periaortic adipose tissue was measured over 16 contiguous slices, covering 40 mm above the aortic bifurcation. The first slice above the aortic bifurcation was defined as the slice where the difference between transversal and anterior-posterior diameter were less than 1 mm.

Figure 1.

Figure 1

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Figure 1 demonstrates schematic the border for periaortic adipose tissue around the abdominal (A) and thoracic (C) aorta and 3D rendered volume of AAT (B) and TAT (D).

We excluded subjects in whom the difference between transverse and anterior-posterior diameter remained >5 mm within the volume of interest because the oval shape of the aorta precluded a standardized measurement of the periaortic adipose tissue cylinder. In addition, we excluded all subjects in whom <40 mm of the aorta above the bifurcation was captured on CT. To account for the linear relationship between the aortic diameter and the area of the abdominal periaortic adipose tissue cylinder (Equation 1), all abdominal periaortic adipose tissue measurements were adjusted for aortic diameter (anterior-posterior diameter, first slice above the bifurcation).

Equation 1.

Equation 1

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Abbreviations: V, volume of perivascular adipose tissue (in mm3; π, Pi (3.14); d, aorta diameter (in mm); c, thickness of the circle around the aorta (5mm); h, height of the total volume (40mm)).

Thoracic periaortic adipose tissue (TAT) protocol

In contrast to the abdominal aorta, thoracic periaortic adipose tissue can be clearly separated from other anatomical structures. Thus, the region of interest included all of the adipose tissue surrounding the thoracic aorta. The volume of interest was extended 67.5 mm below the level of the pulmonary artery bifurcation, which was the highest common denominator for all subjects (Figure 1 C and D). If necessary, manual adjustments were made throughout the analyzed imaging volume. Subjects with hiatal hernia and intra-thoracic stomach were excluded from the analysis.

Subcutaneous (SAT) and visceral (VAT) abdominal adipose protocol

The protocol for the measurements of subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) in abdominal CT scans identifies adipose tissue in a similar threshold based fashion, is highly reproducible, and previously described by our group elsewhere (14).

Statistical evaluation

Inter- and intra-observer reproducibility was assessed using the intra-class correlation coefficient (ICC). A value close to 1 indicates excellent agreement between the two readings. In addition, the significance of the mean difference between the two readings was assessed using the paired t-test.

Spearmann correlation coefficients, adjusted for age and sex using partial correlation, were used to assess relations of periaortic adipose tissue (AAT and TAT) to BMI, WC, SAT, and VAT, as well among each other. In all correlations, AAT volumes were adjusted in addition for aorta diameter, as we detected a linear assocations between SAT and VAT volume and aortic diameter. This is shown in Equation 1. A p-value <0.05 was considered to indicate statistical significance.

Results

This subgroup of the Framingham Heart Study was characterized by an average age of 59.9 ± 12.9 years and an average BMI of 27.8±4.6 (Table 1). The subgroups does not significantly differ from the whole Framingham Offspring cohort with respect to age, gender, BMI and waist circumference (all p>0.25). We excluded 10 subjects from measurements of AAT (10%, one abdominal aneurysm and nine subjects with an oval aorta) but only three from TAT measurements (3%, three hiatal hernia). On average, the evaluation for each subject required six minutes for each measurement.

Table 1.

Demographic characteristics

Variable Mean S.D. Min. Max.
Age 59.9 12.9 37 83
Weight (kg) 79.6 16.2 48.5 137.0
Height (cm) 169.0 9.2 150.5 190.5
BMI (kg/m2) 27.8 4.6 18.2 41.6
Waist Circumference (WC, in cm) 99.1 12.5 71.8 132.1
Subcutaneous Adipose Tissue (SAT, in cm3) 2931 1260 501 6695
Visceral Adipose Tissue (VAT, in cm3) 2030 1014 289 4731
Abdominal Periaortic Adipose Tissue (AAT, in cm3) 6.38 3.18 0.08 14.12
Thoracic Periaortic Adipose Tissue (TAT, in cm3) 16.33 8.70 3.70 42.56
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Abbreviations: S.D., standard deviation; BMI, Body-Mass-Index

The mean AAT was 6.38±3.18 cm3 (range: 0.08–14.12 cm3) and the mean TAT was 16.34±8.70 cm3 (range: 3.70–42.56 cm3). AAT and TAT were highly correlated (r=0.70, p<0.0001).

Intra-observer variability

The intra-observer agreement was excellent for both AAT (ICC=0.970; 95%-CI: 0.954–0.980) and TAT (ICC=0.986; 95%-CI: 0.979–0.991). Both the mean absolute and relative intra-observer differences were small for both AAT: – 0.08±0.08 cm3, p=0.32 and 1.85±1.28%; respectively and TAT: 0.55±0.14 cm3, p=0.0002; 3.56±0.83%; respectively. The significance in the TAT measurement can be explained as a statistical artifact and is due to the very small variation. However, although statistically significant, this finding can be attributed to the small variation of differences between the two observers rather than practically relevant variations of the measurement (13).

Inter-observer variability

Similarly, the variability between the two observers was small for both absolute and relative differences (AAT: 0.11±0.09 cm3, p=0.20 and 7.85±6.08%; respectively; TAT: −0.74±0.14 cm3, p<0.0001 and −4.56±0.85%; respectively). Excellent inter-observer agreement was found between the two observers for AAT (ICC=0.968; 95%-CI: 0.951–0.979) and for TAT (ICC=0.983; 95%-CI: 0.975–0.989).

Relation of periaortic adipose tissue to VAT, SAT, BMI and WC

After adjustment for age and sex as covariates, both AAT and TAT were highly correlated with VAT (AAT: r=0.69, p<0.0001; TAT: r=0.81, p<0.0001), and moderately correlated with SAT (AAT: r=0.43, p<0.0001; TAT: r=0.51, p<0.0001). Correlations of AAT and TAT to BMI and WC are presented in Table 2.

Table 2.

Age and sex adjusted correlation between TAT and AAT with BMI, WC, SAT and VAT

BMI
WC
SAT
VAT
R p R p R p R p
AAT* 0.52 <.0001 0.48 <.0001 0.43 <.0001 0.69 <.0001
TAT 0.69 <.0001 0.62 <.0001 0.51 <.0001 0.81 <.0001
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Abbreviations: r, Spearmann correlation coefficient; p, significance level; TAT, Thoracic Perivascular Adipose Tissue; AAT, Abdominal Perivascular Adipose Tissue; BMI, Body-Mass-Index; WC, waist circumference; SAT, subcutaneous adipose tissue; VAT, visceral adipose tissue,

*

abdominal periaortic adipose tissue additionally adjusted for aortic diameter

Discussion

Principal Findings

In this study we developed standardized protocols for volumetric quantification of abdominal and thoracic periaortic adipose tissue, in non-contrast enhanced MDCT exams in a community-based sample. Our results demonstrate measurements of AAT and TAT are feasible and highly reproducible. Moreover, the extent of periaortic adipose tissue is associated with anthropometric measures (BMI and WC) and abdominal fat depots (VAT and SAT).

The average amount of abdominal periaortic adipose tissue (AAT) was smaller than of thoracic periaortic adipose tissue (TAT), most likely due to the difference in volume coverage (AAT: 40mm, TAT: 67.5mm) of the two protocols. Despite the relatively small adipose tissue volumes both AAT and TAT had a coefficient of variation of about 50% (TAT: 53.3%; AAT of 49.9%), which were similar to SAT and VAT (43.0% and 49.9%, retrospectively) but much larger when compared to BMI or WC (16.5% and 12.6%, retrospectively), indicating a substantial amount of individual variation of these measurements.

In the Context of the Current Literature

Prior studies have established standardized highly reproducible protocols of MDCT-based volumetric quantification of visceral and subcutaneous adipose tissue and pericardial fat (12, 13, 23). In contrast, CT measurements of periaortic adipose tissue, another potentially important local fat depot, have not been described.

Our study introduces two protocols for periaortic fat measurements. While we demonstrated that both are highly reliable and reproducible, it is important to highlight some methodological considerations. While the identification of thoracic periaortic adipose tissue is straightforward, it is a challenge to clearly separate periaortic adipose tissue from retroperitoneal fat poses. This is important because the blood supply of perivascular fat drains directly into the vasa vasorum potentially exerting local effects on the aorta. In order to capture perivascular fat we measured a cylinder of adipose tissue extending five mm around the aorta (12, 15).

Potential Significance of perivascular adipose tissue for cardiovascular disease

The rationale for our study is based on the recognition that adipose tissue is a multifunctional endocrine organ (24), which can store lipids but also secrete hormones, adipocytokines, and proinflammatory substances (25, 26). Adipocytokines, macrophages and neutrophils including adiponectin and leptin, have been isolated from perivascular adipose tissue (27, 28), suggesting that perivascular adipose tissue may have a paracrine effect on the vessel wall (29). Consistent with these findings, pericardial fat is associated with coronary calcification (17) and the angiographic extent of coronary artery disease (30, 31).

We demonstrate significant correlations of periaortic adipose tissue with CT-based volumetric measurements of VAT and SAT as well to anthropometric measures of obesity including BMI and WC. Interestingly, the highest correlations were observed with VAT, followed by BMI and WC, and SAT. Ultimately, the importance of AAT and TAT will be determined in association with aortic calcification, pericardial fat and coronary calcification in larger cohorts. Furthermore, outcome studies need to establish whether perivascular adipose tissue depots have prognostic significance and could provide additional evidence for a causal relationship.

Strengths and Limitations

The strength of this study is the development of a standardized semiautomatic measurement for novel measures of AAT and TAT which is feasible and highly reproducible. This protocol was developed within the Framingham Heart Study sample, a well-characterized population-based study. Limitations include the radiation exposure associated with computed tomography and the difficulties to define anatomic regions in non-contrast computed tomography.

Implications

This study lays the foundation for further investigations of the association between periaortic adipose tissue with cardiometabolic risk factors, subclinical CVD, and CVD.

Conclusion

Standardized semiautomatic CT-based volumetric quantification of periaortic adipose tissue is feasible and highly reproducible. The close correlation to other measures of obesity warrants further investigation regarding their association with other body fat deposits, cardiovascular risk factors, vascular disease and clinical outcomes.

Figure 2.

Figure 2

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Histogram of Abdominal Periaortic Adipose Tissue (a) and Thoracic Periaortic Adipose Tissue (b).

Figure 3.

Figure 3

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Reproducibility of Abdominal Periaortic Adipose Tissue (AAT), Intra-and Inter-observer correlation with absolute mean difference (ICC = 0.97, −0.08±0.08cm3 (A); ICC = 0.97, 0.11 ± 0.09 cm3 (B), respectively) and of Thoracic Periaortic Adipose Tissue (TAT), Intra-and Inter-observer with absolute mean differences (ICC = 0.99, 0.55±0.14 cm3 (C); ICC = 0.98, −0.74±0.14cm3 (D), respectively)

Acknowledgments

This work was supported by the National Heart, Lung and Blood Institute’s Framingham Heart Study (N01-HC-25195).

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