Assessment of atherosclerotic plaque activity in patients with sleep apnea using hybrid positron emission tomography/magnetic resonance imaging (PET/MRI): a feasibility study



Evidence suggests that the inflammatory state of an atherosclerotic plaque is important in predicting future risk of plaque rupture. This study aims to investigate the feasibility of measuring plaque inflammation in patients with obstructive sleep apnea (OSA) utilizing advanced vascular imaging — hybrid positron-emission tomography/magnetic resonance imaging (PET/MRI) with fluorodeoxyglucose (FDG) tracer—before and after continuous positive airway pressure (CPAP).


Patients with newly diagnosed moderate to severe OSA underwent baseline PET/MRI for assessment of vascular inflammation of the carotid arteries and thoracic aorta prior to initiation of CPAP. Those adherent to CPAP returned for repeat imaging after 3–6 months of CPAP use. Atherosclerotic plaque activity, as measured by arterial wall FDG uptake, was calculated using target-to-background ratios (TBR) before and after CPAP.


Five patients were recruited as part of a focused project. Mean age was 52 years (80% male), and mean apnea-hypopnea index (AHI) was 33. Three patients were objectively adherent with CPAP. In the pre-CPAP phase, all patients had focal FDG uptake in the carotid arteries and aorta. After CPAP, there was an average reduction in TBR of 5.5% (TBRmean) and 6.2% (TBRmax) in carotid and aortic plaque inflammation, similar in magnitude to the reduction observed with statin therapy alone in non-OSA patients (previously reported by others).


We demonstrate the feasibility of using hybrid PET/MRI to assess atherosclerotic plaque inflammation in patients with OSA before and after CPAP. Use of the vascular PET/MRI platform in patients with OSA may provide better insight into the role of OSA and its treatment in reducing atherosclerotic inflammation.

This is a preview of subscription content, access via your institution.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5


  1. 1.

    Peppard PE, Young T, Barnet JH, Palta M, Hagen EW, Hla KM (2013) Increased prevalence of sleep-disordered breathing in adults. Am J Epidemiol 177(9):1006–1014.

    Article  PubMed  PubMed Central  Google Scholar 

  2. 2.

    Drager LF, Bortolotto LA, Figueiredo AC, Krieger EM, Lorenzi GF (2007) Effects of continuous positive airway pressure on early signs of atherosclerosis in obstructive sleep apnea. Am J Respir Crit Care Med 176(7):706–712.

    CAS  Article  Google Scholar 

  3. 3.

    Drager LF, Bortolotto LA, Krieger EM, Lorenzi-Filho G (2009) Additive effects of obstructive sleep apnea and hypertension on early markers of carotid atherosclerosis. Hypertension 53(1):64–69.

    CAS  Article  PubMed  Google Scholar 

  4. 4.

    Drager LF, Bortolotto LA, Lorenzi MC, Figueiredo AC, Krieger EM, Lorenzi-Filho G (2005) Early signs of atherosclerosis in obstructive sleep apnea. Am J Respir Crit Care Med 172(5):613–618.

    Article  PubMed  Google Scholar 

  5. 5.

    Drager LF, Polotsky VY, Lorenzi-Filho G (2011) Obstructive sleep apnea: an emerging risk factor for atherosclerosis. Chest 140(2):534–542.

    Article  PubMed  PubMed Central  Google Scholar 

  6. 6.

    Javaheri S, Barbe F, Campos-Rodriguez F, Dempsey JA, Khayat R, Javaheri S, Malhotra A, Martinez-Garcia MA, Mehra R, Pack AI, Polotsky VY, Redline S, Somers VK (2017) Sleep apnea: types, mechanisms, and clinical cardiovascular consequences. J Am Coll Cardiol 69(7):841–858.

    Article  PubMed  PubMed Central  Google Scholar 

  7. 7.

    Ambrose JA, Tannenbaum MA, Alexopoulos D, Hjemdahl-Monsen CE, Leavy J, Weiss M, Borrico S, Gorlin R, Fuster V (1988) Angiographic progression of coronary artery disease and the development of myocardial infarction. J Am Coll Cardiol 12(1):56–62.

    CAS  Article  PubMed  Google Scholar 

  8. 8.

    Little WCCM, Applegate RJ, Kutcher MA, Burrows MT, Kahl FR, Santamore WP (1988) Can coronary angiography predict the site of a subsequent myocardial infarction in patients with mild-to-moderate coronary artery disease? Circulation 78(5):1157–1166

    CAS  Article  Google Scholar 

  9. 9.

    Tarkin JM, Joshi FR, Rudd JH (2014) PET imaging of inflammation in atherosclerosis. Nat Rev Cardiol 11(8):443–457.

    CAS  Article  PubMed  Google Scholar 

  10. 10.

    Woollard KJ, Geissmann F (2010) Monocytes in atherosclerosis: subsets and functions. Nat Rev Cardiol 7(2):77–86.

    Article  PubMed  PubMed Central  Google Scholar 

  11. 11.

    Moreno PR, Falk E, Palacios IF, Newell JB, Fuster V, Fallon JT (1994) Macrophage infiltration in acute coronary syndromes. Implications for plaque rupture. Circulation 90(2):775–778

    CAS  Article  Google Scholar 

  12. 12.

    Tawakol A, Migrino RQ, Bashian GG, Bedri S, Vermylen D, Cury RC, Yates D, LaMuraglia GM, Furie K, Houser S, Gewirtz H, Muller JE, Brady TJ, Fischman AJ (2006) In vivo 18F-fluorodeoxyglucose positron emission tomography imaging provides a noninvasive measure of carotid plaque inflammation in patients. J Am Coll Cardiol 48(9):1818–1824.

    Article  PubMed  Google Scholar 

  13. 13.

    Garedew A, Henderson SO, Moncada S (2010) Activated macrophages utilize glycolytic ATP to maintain mitochondrial membrane potential and prevent apoptotic cell death. Cell Death Differ 17(10):1540–1550.

    CAS  Article  PubMed  Google Scholar 

  14. 14.

    Kubota R, Kubota K, Yamada S, Tada M, Ido T, Tamahashi N (1994) Microautoradiographic study for the differentiation of intratumoral macrophages, granulation tissues and cancer cells by the dynamics of fluorine-18-fluorodeoxyglucose uptake. J Nucl Med 35(1):104–112

    CAS  PubMed  Google Scholar 

  15. 15.

    Evans NR, Tarkin JM, Chowdhury MM, Warburton EA, Rudd JH (2016) PET imaging of atherosclerotic disease: advancing plaque assessment from anatomy to pathophysiology. Curr Atheroscler Rep 18(6):30.

    Article  PubMed  PubMed Central  Google Scholar 

  16. 16.

    Rudd JHF (2002) Imaging atherosclerotic plaque inflammation with [18F]-Fluorodeoxyglucose positron emission tomography. Circulation 105(23):2708–2711.

    CAS  Article  PubMed  Google Scholar 

  17. 17.

    Marnane M, Merwick A, Sheehan OC, Hannon N, Foran P, Grant T, Dolan E, Moroney J, Murphy S, O'Rourke K, O'Malley K, O'Donohoe M, McDonnell C, Noone I, Barry M, Crowe M, Kavanagh E, O'Connell M, Kelly PJ (2012) Carotid plaque inflammation on 18F-fluorodeoxyglucose positron emission tomography predicts early stroke recurrence. Ann Neurol 71(5):709–718.

    Article  PubMed  Google Scholar 

  18. 18.

    Paulmier B, Duet M, Khayat R, Pierquet-Ghazzar N, Laissy JP, Maunoury C, Hugonnet F, Sauvaget E, Trinquart L, Faraggi M (2008) Arterial wall uptake of fluorodeoxyglucose on PET imaging in stable cancer disease patients indicates higher risk for cardiovascular events. J Nucl Cardiol 15(2):209–217.

    Article  PubMed  Google Scholar 

  19. 19.

    Rominger A, Saam T, Wolpers S, Cyran CC, Schmidt M, Foerster S, Nikolaou K, Reiser MF, Bartenstein P, Hacker M (2009) 18F-FDG PET/CT identifies patients at risk for future vascular events in an otherwise asymptomatic cohort with neoplastic disease. J Nucl Med 50(10):1611–1620.

    Article  PubMed  Google Scholar 

  20. 20.

    Figueroa AL, Abdelbaky A, Truong QA, Corsini E, MacNabb MH, Lavender ZR, Lawler MA, Grinspoon SK, Brady TJ, Nasir K, Hoffmann U, Tawakol A (2013) Measurement of arterial activity on routine FDG PET/CT images improves prediction of risk of future CV events. JACC Cardiovasc Imaging 6(12):1250–1259.

    Article  PubMed  Google Scholar 

  21. 21.

    Tahara N, Kai H, Ishibashi M, Nakaura H, Kaida H, Baba K, Hayabuchi N, Imaizumi T (2006) Simvastatin attenuates plaque inflammation: evaluation by fluorodeoxyglucose positron emission tomography. J Am Coll Cardiol 48(9):1825–1831.

    CAS  Article  PubMed  Google Scholar 

  22. 22.

    Gerber BL (2013) In vivo evaluation of atherosclerotic plaque inflammation and of anti-inflammatory effects of statins by 18F-fluorodeoxyglucose positron emission tomography. J Am Coll Cardiol 62(10):918–920.

    Article  PubMed  Google Scholar 

  23. 23.

    Tawakol A, Fayad ZA, Mogg R, Alon A, Klimas MT, Dansky H, Subramanian SS, Abdelbaky A, Rudd JH, Farkouh ME, Nunes IO, Beals CR, Shankar SS (2013) Intensification of statin therapy results in a rapid reduction in atherosclerotic inflammation. results of a multicenter fluorodeoxyglucose-positron emission tomography/computed tomography feasibility study J Am Coll Cardiol 62(10):909–917.

    CAS  Article  PubMed  Google Scholar 

  24. 24.

    Johns MW (1991) A new method for measuring daytime sleepiness: the Epworth sleepiness scale. Sleep 14(6):540–545

    CAS  Article  Google Scholar 

  25. 25.

    Berry RB BR, Gamaldo CE, Harding SM, Lloyd RM, Marcus CL, Vaughn BV (2015) The AASM manual for the scoring of sleep and associated events: rules, terminology, and technical specifications. Am Acad Sleep Med Version 2.2

  26. 26.

    Berry RB, Brooks R, Gamaldo C, Harding SM, Lloyd RM, Quan SF, Troester MT, Vaughn BV (2017) AASM scoring manual updates for 2017 (version 2.4). J Clin Sleep Med 13(5):665–666.

    Article  PubMed  PubMed Central  Google Scholar 

  27. 27.

    Vesey AT, Dweck MR, Fayad ZA (2016) Utility of combining PET and MR imaging of carotid plaque. Neuroimaging Clin N Am 26(1):55–68.

    Article  PubMed  Google Scholar 

  28. 28.

    Robson PM, Dweck MR, Trivieri MG, Abgral R, Karakatsanis NA, Contreras J, Gidwani U, Narula JP, Fuster V, Kovacic JC, Fayad ZA (2017) Coronary artery PET/MR imaging: feasibility, limitations, and solutions. JACC Cardiovasc Imaging 10(10 Pt A):1103–1112.

    Article  PubMed  PubMed Central  Google Scholar 

  29. 29.

    Rudd JH, Myers KS, Bansilal S, Machac J, Rafique A, Farkouh M, Fuster V, Fayad ZA (2007) (18)Fluorodeoxyglucose positron emission tomography imaging of atherosclerotic plaque inflammation is highly reproducible: implications for atherosclerosis therapy trials. J Am Coll Cardiol 50(9):892–896.

    Article  PubMed  Google Scholar 

  30. 30.

    Bucerius J, Hyafil F, Verberne HJ, Slart RH, Lindner O, Sciagra R, Agostini D, Ubleis C, Gimelli A, Hacker M, Cardiovascular Committee of the European Association of Nuclear M (2016) Position paper of the cardiovascular Committee of the European Association of nuclear medicine (EANM) on PET imaging of atherosclerosis. Eur J Nucl Med Mol Imaging 43(4):780–792.

    Article  PubMed  Google Scholar 

  31. 31.

    Rudd JH, Myers KS, Bansilal S, Machac J, Pinto CA, Tong C, Rafique A, Hargeaves R, Farkouh M, Fuster V, Fayad ZA (2008) Atherosclerosis inflammation imaging with 18F-FDG PET: carotid, iliac, and femoral uptake reproducibility, quantification methods, and recommendations. J Nucl Med 49(6):871–878.

    Article  PubMed  Google Scholar 

  32. 32.

    CMS (2016) Positive Airway Pressure (PAP) Devices: complying with documentation & coverage requirements. US Department of Health and Human Services; Center for Medicare and Medicaid Services (CMS)

  33. 33.

    Wilson PW, D'Agostino RB, Levy D, Belanger AM, Silbershatz H, Kannel WB (1998) Prediction of coronary heart disease using risk factor categories. Circulation 97(18):1837–1847

    CAS  Article  Google Scholar 

  34. 34.

    Goff DC, Lloyd-Jones DM, Bennett G, Coady S, D’Agostino RB, Gibbons R, Greenland P, Lackland DT, Levy D, O’Donnell CJ, Robinson JG, Schwartz JS, Shero ST, Smith SC, Sorlie P, Stone NJ, Wilson PWF (2014) 2013 ACC/AHA guideline on the assessment of cardiovascular risk. J Am Coll Cardiol 63(25):2935–2959.

    Article  PubMed  Google Scholar 

  35. 35.

    Kim J, Mohler ER 3rd, Keenan BT, Maislin D, Arnardottir ES, Gislason T, Benediktsdottir B, Gudmundsdottir S, Sifferman A, Staley B, Pack FM, Maislin G, Chirinos JA, Townsend RR, Pack AI, Kuna ST (2017) Carotid Artery Wall thickness in obese and nonobese adults with obstructive sleep apnea before and following positive airway pressure treatment. Sleep 40(9).

  36. 36.

    Polak JF, Pencina MJ, Pencina KM, O'Donnell CJ, Wolf PA, D'Agostino RB Sr (2011) Carotid-wall intima-media thickness and cardiovascular events. N Engl J Med 365(3):213–221.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  37. 37.

    Inaba Y, Chen JA, Bergmann SR (2012) Carotid plaque, compared with carotid intima-media thickness, more accurately predicts coronary artery disease events: a meta-analysis. Atherosclerosis 220(1):128–133.

    CAS  Article  PubMed  Google Scholar 

  38. 38.

    Nambi V, Chambless L, Folsom AR, He M, Hu Y, Mosley T, Volcik K, Boerwinkle E, Ballantyne CM (2010) Carotid intima-media thickness and presence or absence of plaque improves prediction of coronary heart disease risk: the ARIC (atherosclerosis risk in communities) study. J Am Coll Cardiol 55(15):1600–1607.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  39. 39.

    Costanzo P, Perrone-Filardi P, Vassallo E, Paolillo S, Cesarano P, Brevetti G, Chiariello M (2010) Does carotid intima-media thickness regression predict reduction of cardiovascular events? A meta-analysis of 41 randomized trials. J Am Coll Cardiol 56(24):2006–2020.

    Article  PubMed  Google Scholar 

  40. 40.

    Kylintireas I, Craig S, Nethononda R, Kohler M, Francis J, Choudhury R, Stradling J, Neubauer S (2012) Atherosclerosis and arterial stiffness in obstructive sleep apnea—a cardiovascular magnetic resonance study. Atherosclerosis 222(2):483–489.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  41. 41.

    Sluimer JC, Gasc JM, van Wanroij JL, Kisters N, Groeneweg M, Sollewijn Gelpke MD, Cleutjens JP, van den Akker LH, Corvol P, Wouters BG, Daemen MJ, Bijnens AP (2008) Hypoxia, hypoxia-inducible transcription factor, and macrophages in human atherosclerotic plaques are correlated with intraplaque angiogenesis. J Am Coll Cardiol 51(13):1258–1265.

    CAS  Article  PubMed  Google Scholar 

  42. 42.

    Davignon J (2004) Beneficial cardiovascular pleiotropic effects of statins. Circulation 109(23 Suppl 1):III39–III43.

    CAS  Article  PubMed  Google Scholar 

  43. 43.

    Kohler M, Stradling JR (2010) Mechanisms of vascular damage in obstructive sleep apnea. Nat Rev Cardiol 7(12):677–685.

    Article  PubMed  Google Scholar 

  44. 44.

    Curry BD, Bain JL, Yan JG, Zhang LL, Yamaguchi M, Matloub HS, Riley DA (2002) Vibration injury damages arterial endothelial cells. Muscle Nerve 25(4):527–534

    Article  Google Scholar 

  45. 45.

    Lee SA, Amis TC, Byth K, Larcos G, Kairaitis K, Robinson TD, Wheatley JR (2008) Heavy snoring as a cause of carotid artery atherosclerosis. Sleep 31(9):1207–1213

    PubMed  PubMed Central  Google Scholar 

  46. 46.

    Puig F, Rico F, Almendros I, Montserrat JM, Navajas D, Farre R (2005) Vibration enhances interleukin-8 release in a cell model of snoring-induced airway inflammation. Sleep 28(10):1312–1316

    Article  Google Scholar 

  47. 47.

    Lee GS, Lee LA, Wang CY, Chen NH, Fang TJ, Huang CG, Cheng WN, Li HY (2016) The frequency and energy of snoring sounds are associated with common carotid artery intima-media thickness in obstructive sleep apnea patients. Sci Rep 6:30559.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  48. 48.

    Kuna ST, Gurubhagavatula I, Maislin G, Hin S, Hartwig KC, McCloskey S, Hachadoorian R, Hurley S, Gupta R, Staley B, Atwood CW (2011) Noninferiority of functional outcome in ambulatory management of obstructive sleep apnea. Am J Respir Crit Care Med 183(9):1238–1244.

    Article  PubMed  Google Scholar 

  49. 49.

    Rosen CL, Auckley D, Benca R, Foldvary-Schaefer N, Iber C, Kapur V, Rueschman M, Zee P, Redline S (2012) A multisite randomized trial of portable sleep studies and positive airway pressure autotitration versus laboratory-based polysomnography for the diagnosis and treatment of obstructive sleep apnea: the HomePAP study. Sleep 35(6):757–767.

    Article  PubMed  PubMed Central  Google Scholar 

  50. 50.

    Berry RB, Sriram P (2014) Auto-adjusting positive airway pressure treatment for sleep apnea diagnosed by home sleep testing. J Clin Sleep Med 10(12):1269–1275.

    Article  PubMed  PubMed Central  Google Scholar 

  51. 51.

    van der Valk FM, Verweij SL, Zwinderman KA, Strang AC, Kaiser Y, Marquering HA, Nederveen AJ, Stroes ES, Verberne HJ, Rudd JH (2016) Thresholds for Arterial Wall inflammation quantified by 18F-FDG PET imaging: implications for Vascular Interventional Studies. JACC Cardiovasc Imaging 9(10):1198–1207.

    Article  PubMed  PubMed Central  Google Scholar 

  52. 52.

    McEvoy RD, Antic NA, Heeley E, Luo Y, Ou Q, Zhang X, Mediano O, Chen R, Drager LF, Liu Z, Chen G, Du B, McArdle N, Mukherjee S, Tripathi M, Billot L, Li Q, Lorenzi-Filho G, Barbe F, Redline S, Wang J, Arima H, Neal B, White DP, Grunstein RR, Zhong N, Anderson CS, Investigators S, Coordinators (2016) CPAP for prevention of cardiovascular events in obstructive sleep apnea. N Engl J Med 375(10):919–931.

    Article  PubMed  Google Scholar 

Download references


The study was supported by the American Sleep Medicine Foundation Focused Project Award (126-FP-15) and Dr. Shah has funding from the National Institute of Health/National Heart, Lung, and Blood Institute Research Career Development Award (5K23HL125923-03). The authors report no conflicts of interest. All authors have read and approved the submitted manuscript.


The American Sleep Medicine Foundation provided financial support in the form of the Focused Project Award (126-FP-15) funding. Dr. Shah also has funding from the National Institute of Health/National Heart, Lung, and Blood Institute Research Career Development Award (5K23HL125923-03). The sponsor had no role in the design or conduct of this award.

Author information



Corresponding author

Correspondence to Neomi Shah.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of Icahn School of Medicine at Mount Sinai and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Kundel, V., Trivieri, M.G., Karakatsanis, N.A. et al. Assessment of atherosclerotic plaque activity in patients with sleep apnea using hybrid positron emission tomography/magnetic resonance imaging (PET/MRI): a feasibility study. Sleep Breath 22, 1125–1135 (2018).

Download citation


  • Obstructive sleep apnea
  • CPAP
  • Atherosclerosis
  • Plaque
  • Inflammation