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Vascular inflammation in psoriasis localizes to the arterial wall using a novel imaging technique
LETTER RESEARCH Vascular inflammation in psoriasis localizes to the arterial wall using a novel imaging technique To the Editor: Metabolic positron emission tomography (PET) imaging with the glucose analog 18F-fluorodeoxyglucose (FDG) is widely used in the field of oncology because FDG accumulates in regions of increased glycolysis and can distinguish malignant tissue from normal neighboring tissues. Given that FDG-PET is taken up by cells in proportion to metabolic activity, it has emerged as a sensitive modality to detect inflammation throughout the body, in various disease states, and in response to therapy. Recently, reports of vascular inflammation detection using FDG-PET have generated intense interest in the role of FDG-PET to assess the severity and extent of atherosclerosis. Compared to alternative imaging modalities, FDG-PET allows noninvasive, real-time in vivo assessment of inflammatory vascular processes and is most commonly coupled to
Fig 1. A fused PET-CT scan at the level of the aortic arch. This image depicts increased FDG uptake at 60 minutes’ uptake time within the aortic arch of a patient with moderate psoriasis and no other cardiovascular risk factors. The orange-red uptake on this color scale corresponds to moderately high uptake of the FDG tracer per the scale provided on the left of the image. J AM ACAD DERMATOL
LETTER low-dose computed tomography (CT) to provide simultaneous anatomic information. FDG activity detected in blood vessels by PET-CT (Fig 1) is associated with cellular infiltration in active, noncalcified, atherosclerotic plaques.1 The description of cell populations associated with vascular FDG uptake is evolving. Populations of B cells, T cells, and macrophages have been linked to FDG uptake.1 Current literature most often associates FDG uptake with concentrations of macrophage-rich areas of lipid-laden plaques and correlates directly with macrophage density.1 Finally, when FDG uptake is increased within blood vessels, the risk of future cardiovascular events is increased.2 In 2012, we used FDG PET-CT to provide the first in vivo human evidence that psoriasis is associated with systemic inflammation as demonstrated by increased FDG uptake in tissues beyond the skin.3 We observed increased FDG uptake in the blood vessels of patients with psoriasis, which
Fig 2. In the same patient as in Fig 1, this image demonstrates a T1-weighted spin echo MRI with suppressed blood signal fused to PET. This image demonstrates that the FDG tracer uptake at 120 minutes has localized to the arterial wall (white arrows). The orange-red uptake on this color scale corresponds to moderately high uptake of the FDG tracer per the scale provided on the left of the image.
1
2 Letter
supports evolving epidemiologic evidence that psoriasis raises cardiovascular risk, including major adverse cardiovascular events (myocardial infarction, stroke, cardiovascular death).4 This observed increase in vascular inflammation was most recently confirmed in a study demonstrating that systemic therapy for psoriasis may decrease vascular inflammation by FDG PET CT,5 and by ultrasonographic techniques such as carotid intimal medial thickness.6 Magnetic resonance imaging (MRI) maintains an advantage over CT for localization of soft tissue structures, including the perivascular space. Therefore, when PET is combined with MRI for simultaneous image acquisition, FDG tracer localization should be more sensitive and specific for vascular inflammation. To test this hypothesis, we began a systematic evaluation of multimodal imaging in a prospective cohort study of psoriasis (NCT01778569) using simultaneous PET-MRI. Here, we present evidence for the first time that inflammation detected in the blood vessels by PET-CT (Fig 1) indeed localizes to the arterial wall when examined by PET-MRI (Fig 2) in a patient with moderate psoriasis and no other cardiovascular risk factors. An advantage of using PET-MRI for localization of vessel wall uptake is that accurate vessel wall images can be acquired without intravenous contrast, which adds significant risk to a diagnostic imaging exam. Because early subclinical atherosclerosis is an arterial wall disease, this finding on PET-MRI highlights the concept that the vascular inflammation observed on FDG PET-CT in psoriasis may in fact represent early atherosclerosis. This ongoing cohort study will further our understanding of arterial wall inflammation, and its relationship to psoriasis severity, response to treatment, and future cardiovascular events. Furthermore, comparison with nondiseased individuals and other disease states such as coronary artery disease and diabetes is the focus of an ongoing study (NCT01934660), which will permit better understanding of potential variation in FDG uptake within the arterial wall. Jenny Dave, MS,a Mark A. Ahlman, MD,b Benjamin N. Lockshin, MD,c David A. Bluemke, MD, PhD,b and Nehal N. Mehta, MD, MSCEa National Heart Lung & Blood Institute,a National Institutes of Health, Clinical Center, Department
J AM ACAD DERMATOL
of Radiology and Imaging Sciences,b Bethesda, Maryland, and DermAssociates, PC,c Silver Spring, Maryland Funding sources: This work was supported by an intramural grant HL-Z-000000 from the National Institutes of Health. Disclosure: The funding sources had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; or preparation, review, or approval of the manuscript. Dr Lockshin is a consultant for Amgen, Abbott, Eli Lilly, and Abbvie. Dr Bluemke has a research agreement with Siemens Medical Systems. Jenny Dave and Dr Mehta have no conflicts of interest to declare. Correspondence to: Nehal N. Mehta, MD, MSCE, Section Chief, Inflammation and Cardiometabolic Diseases, National Institutes of Health, Building 10/CRC 5-5140, Bethesda, MD 20892 E-mail: [email protected] REFERENCES 1. Courtois A, Nusgens BV, Hustinx R, Namur G, Gomez P, Somja J, et al. 18F-FDG uptake assessed by PET/CT in abdominal aortic aneurysms is associated with cellular and molecular alterations prefacing wall deterioration and rupture. J Nucl Med 2013;54: 1740-7. 2. Rominger A, Saam T, Wolpers S, Cyran CC, Schmidt M, Foerster S, et al. 18F-FDG PET/CT identifies patients at risk for future vascular events in an otherwise asymptomatic cohort with neoplastic disease. J Nucl Med 2009;50:1611-20. 3. Mehta NN, Yu Y, Saboury B, Foroughi N, Krishnamoorthy P, Raper A, et al. Systemic and vascular inflammation in patients with moderate to severe psoriasis as measured by [18F]-fluorodeoxyglucose positron emission tomography/ computed tomography (FDG-PET/CT): a pilot study. Arch Dermatol 2011;147:1031-9. 4. Mehta NN, Yu Y, Pinnelas R, Krishnamoorthy P, Shin DB, Troxel AB, et al. Attributable risk estimate of severe psoriasis on major adverse cardiac events. Am J Med 2011;124:775, e1-6. 5. Bissonnette R, Tardif JC, Harel F, Pressacco J, Bolduc C, Guertin MC. Effects of the tumor necrosis factor- antagonist adalimumab on arterial inflammation assessed by positron emission tomography in patients with psoriasis. Circ Cardiovasc Imaging 2013;6:83-90. 6. J okai H, Szakonyi J, Kontar O, Marschalk o M, Szalai K, Karpati S, et al. Impact of effective tumor necrosis factor-alfa inhibitor treatment on arterial intima-media thickness in psoriasis: results of a pilot study. J Am Acad Dermatol 2013;69:523-9. http://dx.doi.org/10.1016/j.jaad.2013.12.043
Fig 1. A fused PET-CT scan at the level of the aortic arch. This image depicts increased FDG uptake at 60 minutes’ uptake time within the aortic arch of a patient with moderate psoriasis and no other cardiovascular risk factors. The orange-red uptake on this color scale corresponds to moderately high uptake of the FDG tracer per the scale provided on the left of the image. J AM ACAD DERMATOL
LETTER low-dose computed tomography (CT) to provide simultaneous anatomic information. FDG activity detected in blood vessels by PET-CT (Fig 1) is associated with cellular infiltration in active, noncalcified, atherosclerotic plaques.1 The description of cell populations associated with vascular FDG uptake is evolving. Populations of B cells, T cells, and macrophages have been linked to FDG uptake.1 Current literature most often associates FDG uptake with concentrations of macrophage-rich areas of lipid-laden plaques and correlates directly with macrophage density.1 Finally, when FDG uptake is increased within blood vessels, the risk of future cardiovascular events is increased.2 In 2012, we used FDG PET-CT to provide the first in vivo human evidence that psoriasis is associated with systemic inflammation as demonstrated by increased FDG uptake in tissues beyond the skin.3 We observed increased FDG uptake in the blood vessels of patients with psoriasis, which
Fig 2. In the same patient as in Fig 1, this image demonstrates a T1-weighted spin echo MRI with suppressed blood signal fused to PET. This image demonstrates that the FDG tracer uptake at 120 minutes has localized to the arterial wall (white arrows). The orange-red uptake on this color scale corresponds to moderately high uptake of the FDG tracer per the scale provided on the left of the image.
1
2 Letter
supports evolving epidemiologic evidence that psoriasis raises cardiovascular risk, including major adverse cardiovascular events (myocardial infarction, stroke, cardiovascular death).4 This observed increase in vascular inflammation was most recently confirmed in a study demonstrating that systemic therapy for psoriasis may decrease vascular inflammation by FDG PET CT,5 and by ultrasonographic techniques such as carotid intimal medial thickness.6 Magnetic resonance imaging (MRI) maintains an advantage over CT for localization of soft tissue structures, including the perivascular space. Therefore, when PET is combined with MRI for simultaneous image acquisition, FDG tracer localization should be more sensitive and specific for vascular inflammation. To test this hypothesis, we began a systematic evaluation of multimodal imaging in a prospective cohort study of psoriasis (NCT01778569) using simultaneous PET-MRI. Here, we present evidence for the first time that inflammation detected in the blood vessels by PET-CT (Fig 1) indeed localizes to the arterial wall when examined by PET-MRI (Fig 2) in a patient with moderate psoriasis and no other cardiovascular risk factors. An advantage of using PET-MRI for localization of vessel wall uptake is that accurate vessel wall images can be acquired without intravenous contrast, which adds significant risk to a diagnostic imaging exam. Because early subclinical atherosclerosis is an arterial wall disease, this finding on PET-MRI highlights the concept that the vascular inflammation observed on FDG PET-CT in psoriasis may in fact represent early atherosclerosis. This ongoing cohort study will further our understanding of arterial wall inflammation, and its relationship to psoriasis severity, response to treatment, and future cardiovascular events. Furthermore, comparison with nondiseased individuals and other disease states such as coronary artery disease and diabetes is the focus of an ongoing study (NCT01934660), which will permit better understanding of potential variation in FDG uptake within the arterial wall. Jenny Dave, MS,a Mark A. Ahlman, MD,b Benjamin N. Lockshin, MD,c David A. Bluemke, MD, PhD,b and Nehal N. Mehta, MD, MSCEa National Heart Lung & Blood Institute,a National Institutes of Health, Clinical Center, Department
J AM ACAD DERMATOL
of Radiology and Imaging Sciences,b Bethesda, Maryland, and DermAssociates, PC,c Silver Spring, Maryland Funding sources: This work was supported by an intramural grant HL-Z-000000 from the National Institutes of Health. Disclosure: The funding sources had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; or preparation, review, or approval of the manuscript. Dr Lockshin is a consultant for Amgen, Abbott, Eli Lilly, and Abbvie. Dr Bluemke has a research agreement with Siemens Medical Systems. Jenny Dave and Dr Mehta have no conflicts of interest to declare. Correspondence to: Nehal N. Mehta, MD, MSCE, Section Chief, Inflammation and Cardiometabolic Diseases, National Institutes of Health, Building 10/CRC 5-5140, Bethesda, MD 20892 E-mail: [email protected] REFERENCES 1. Courtois A, Nusgens BV, Hustinx R, Namur G, Gomez P, Somja J, et al. 18F-FDG uptake assessed by PET/CT in abdominal aortic aneurysms is associated with cellular and molecular alterations prefacing wall deterioration and rupture. J Nucl Med 2013;54: 1740-7. 2. Rominger A, Saam T, Wolpers S, Cyran CC, Schmidt M, Foerster S, et al. 18F-FDG PET/CT identifies patients at risk for future vascular events in an otherwise asymptomatic cohort with neoplastic disease. J Nucl Med 2009;50:1611-20. 3. Mehta NN, Yu Y, Saboury B, Foroughi N, Krishnamoorthy P, Raper A, et al. Systemic and vascular inflammation in patients with moderate to severe psoriasis as measured by [18F]-fluorodeoxyglucose positron emission tomography/ computed tomography (FDG-PET/CT): a pilot study. Arch Dermatol 2011;147:1031-9. 4. Mehta NN, Yu Y, Pinnelas R, Krishnamoorthy P, Shin DB, Troxel AB, et al. Attributable risk estimate of severe psoriasis on major adverse cardiac events. Am J Med 2011;124:775, e1-6. 5. Bissonnette R, Tardif JC, Harel F, Pressacco J, Bolduc C, Guertin MC. Effects of the tumor necrosis factor- antagonist adalimumab on arterial inflammation assessed by positron emission tomography in patients with psoriasis. Circ Cardiovasc Imaging 2013;6:83-90. 6. J okai H, Szakonyi J, Kontar O, Marschalk o M, Szalai K, Karpati S, et al. Impact of effective tumor necrosis factor-alfa inhibitor treatment on arterial intima-media thickness in psoriasis: results of a pilot study. J Am Acad Dermatol 2013;69:523-9. http://dx.doi.org/10.1016/j.jaad.2013.12.043