Measuring Visceral Adipose Tissue Metabolic Activity in Sleep Apnea Utilizing Hybrid ¹⁸F-FDG PET/MRI: A Pilot Study

Figures & data

Figure 1 Visceral (VAT) and subcutaneous (SAT) adipose tissue depots. (A) Subcutaneous and visceral adipose tissue depots in the abdomen. (B) Pathologic/inflamed visceral adipose tissue.

Figure 2 Adipose tissue manual tracing and segmentation. (A) Axial MR slice, with manual tracing of the outer contours of subcutaneous adipose tissue (SAT), performed for each slice from the pelvic floor to the level of the diaphragm. (B) Fat segmentation using a custom-made MATLAB script to perform automated analysis of pixel intensity to discriminate tissue class (visceral adipose tissue [VAT] in the abdomen from other organs). Adipose tissue areas from each slice were then summed across the abdomen for total SAT and VAT volumes. (C) Adipose tissue FDG uptake was measured using standardized uptake values (SUV) within the segmented VAT and SAT compartments of each analyzed slice, excluding organ (renal) FDG uptake.

Abbreviations: FDG, fluorodeoxyglucose; MR, magnetic resonance; PET, positron emission tomography; VAT, visceral adipose tissue.

Table 1 Patient Demographics and Outcome Measures by Sleep Apnea Severity

Demographics	Total Sample (n = 16)	OSA Category (RDI 4%)		p-value
		Mild OSA (n = 7)	Moderate to Severe OSA (n = 9)
Mean Age, (SD)	47.3 (15)	44.1 (10.7)	49.7 (18.1)	0.49
Mean BMI (SD)	29.9 (4.8)	29.5 (3.2)	30.2 (6.0)	0.79
Male (n, %)	13, 81%	5, 71%	8, 89%	0.37
Race (n, %)				0.53
White	9, 56%	4, 57%	5, 56%
Black	2, 13%	1, 14%	1, 11%
Other	5, 31%	2, 29%	3, 33%
Ethnicity – Hispanic (n, %)	6, 38%	4, 57%	2, 22%	0.15
HTN (n, %)	6, 38%	1, 14%	5, 56%	0.09
DM (n, %)	1, 6%	1, 14%	0, 0%	0.25
Sleep Apnea Severity
Mean RDI 4% (SD)	16.5 (8.6)	8.7 (3.7)	22.6 (5.7)	<0.0001
CPAP Compliance
Mean hours used on days used (SD)	5.6 (1.9)	4.7 (2.3)	6.2 (1.2)	0.10
**Percent of days >4 hours use (IQR)	71 (43, 94)	51 (6, 87)	86 (63, 96)	0.14
Mean number of days used (SD)	77.8 (28.1)	65.4 (30.6)	87.4 (23.2)	0.12
Mean AHI on CPAP (SD)	4.0 (2.5)	4.0 (2.9)	3.9 (2.5)
Outcome Measures (Visit 1)
Mean VAT SUVmean (SD)	0.71 (0.19)	0.602 (0.19)	0.795 (0.154)	0.04
Mean VAT Volume (SD)	3684 cm^3 (1523)	3181cm^3 (1406)	4075cm^3 (1573)	0.26
**SAT SUVmean (IQR)	0.302 (0.27, 0.34)	0.30 (0.20, 37)	0.307 (0.28, 0.33)	0.54
**SAT Volume (IQR)	3140 cm^3 (2333, 4763)	3077 cm^3 (1963, 5308)	3203 cm^3 (2375, 4219)	0.76
VAT/SAT Volume ratio (SD)	1.19 (0.65)	1.11 (0.60)	1.25 (0.71)	0.70
†VAT SUVmean*VAT Volume	2598 (1075)	1991 (1148)	3070 (779)	0.04

Notes: Mild OSA 5≤RDI<15, moderate-to-severe RDI ≥15 events/hour. **Median (IQR) reported; †VAT SUVmean multiplied by VAT volume; p-values in bold denote statistical significance (alpha <0.05).

Abbreviations: AHI, Apnea Hypopnea Index; BMI, body mass index; CPAP, continuous positive airway pressure; IQR, interquartile range; OSA, obstructive sleep apnea; RDI, Respiratory Disturbance Index with 4% oxygen desaturations or arousals; SD, standard deviation; SUV, standardized uptake value; SAT, subcutaneous adipose tissue; VAT, visceral adipose tissue.

Table 2 Multivariable Linear Regression – VAT Inflammation and Sleep Apnea Severity (Continuous)

Outcomes	Continuous Per 1 Unit Increase in RDI (OSA Severity)	p for Linear Trend
VAT Inflammation (SUVmean)	B Estimate (SE)
Model 1	0.012 (0.005)	0.03
Model 2	0.013 (0.005)	0.03
VAT Volume (cm^3)
Model 1	−2.67 (47.6)	0.96
Model 2	−22.9 (40.0)	0.58

Notes: p-values in bold denote statistical significance (alpha <0.05), Model 1: Unadjusted, Model 2: Adjusted for age, BMI.

Abbreviations: OSA, obstructive sleep apnea; RDI, Respiratory Disturbance Index with 4% oxygen desaturation or arousal; SE, standard error; SUV, standardized uptake value; VAT, visceral adipose tissue.

Table 3 Change in Outcomes by CPAP Adherence

CPAP Compliance
	Total Sample Median (IQR)	*CPAP Adherent (n = 8), Median (IQR)	CPAP Non-Adherent (n=8), Median (IQR)	p-value
Hours used on days used	5.4 (4.8, 71)	7.1 (6.2, 7.6)	4.8 (3.2, 5.2)	0.0005
Percent of days >4 hours use	71 (43, 94)	93.6 (86, 97)	43.1 (21, 57)	0.0002
Number of days used	88.5 (62, 92.5)	92.5 (91.5, 98.5)	62 (42, 79)	0.002
Outcomes (by CPAP compliance)
	Total Sample, Median Change (IQR)	*CPAP Adherent (n = 8), Median Change (IQR)	CPAP Non-Adherent (n = 8), Median Change (IQR)	p-value
BMI	0.15 (−0.15, 55)	0.0 (−0.5, 0.7)	0.40 (0.1, 0.55)	0.33
VAT SUVmean	0.028 (−0.12, 0.09)	0.028 (−0.05, 0.08)	−0.022 (−0.15, 0.25)	0.98
VAT Volume	−14.8 (−109.5, 90.7)	−52.6 (−179.8, −14.8)	87.5 (−13.5, 118.4)	0.07
SAT SUVmean	0.036 (−0.05, 0.05)	0.037 (0.03, 0.05)	0.019 (−0.06, 0.09)	0.82
SAT Volume	144.10 (−21.0, 237.1)	144.1 (−22.1, 339.1)	147.8 (31.2, 215.8)	0.96

Notes: *CPAP adherence defined as >4 hours usage per night for 70% of the nights over 30 days based on Center for Medicare and Medicaid criteria; p-values in bold denote statistical significance (alpha <0.05).

Abbreviations: BMI, body mass index; CPAP, continuous positive airway pressure; IQR, interquartile range; SUV, standardized uptake Value; SAT, subcutaneous adipose tissue; VAT, visceral adipose tissue.

Figure 3 Change in VAT volume vs CPAP adherence (mean hours/day). Change in VAT volume was inversely correlated with CPAP adherence.

Abbreviations: CPAP, continuous positive airway pressure; CI, confidence intervals; SE, standard error; VAT, visceral adipose tissue.