Vascular Imaging Research Center

You name a vessel, we'll image it! We apply advanced cardiovascular imaging techniques to a range of diseases with the practical goal of improving clinical management. See "Projects" below for details about our research. 

People

Research Team

David A. Saloner, PhD
Professor of Radiology
david.saloner@ucsf.edu
https://www.researchgate.net/profile/David_Saloner

 


Michael D. Hope, MD
Associate Professor of Radiology
 

Jing Liu, PhD
Assistant Adjunct Professor
Data acquisition techniques; Image reconstruction algorithms; 4D MR imaging

 


Chengcheng Zhu, PhD
Postdoctoral Fellow
Black blood vessel wall MRI; Strain and molecular imaging; Cardiac MRI; Image processing
 

Henrik Haraldsson, PhD
Postdoctoral Scholar
https://www.researchgate.net/profile/Henrik_Haraldsson

 


Sarah Kefayati, PhD
Postdoctoral Researcher
Fluid Mechanics, Complex Flows, Turbulence Imaging, MR Flow Imaging, Particle Image Velocimetry
https://scholar.google.com/citations?user=8fUmloIAAAAJ&hl=en


Mehrzad Tartibi, PhD
Postdoctoral Fellow
mtartibi@berkeley.edu
Analytical and numerical modeling of fluid and solid interaction; AAA disease; Intracranial aneurysm; Myocardial disease

Florent Seguro, MD
Postdoctoral Scholar
Advanced cardiovascular imaging (echocardiography and MRI)
 

Evan Kao, BS
Doctoral Student
evan.kao@ucsf.edu
Computational Fluid Dynamics, Fluid-Structure Interaction, Data Visualization, Image Processing, Computational Geometry


Nicholas Burris, MD
Clinical Fellow
Advanced Aortic Imaging, Aortic Dissection, Hemodynamic Imaging
https://scholar.google.com/citations?user=VgzCYpoAAAAJ&hl=en


Kanae Mukai, MD
Clinical Fellow
Cardiac MRI, Mitral Regurgitation
 

Yan, Wang PhD
Postdoctoral Scholar
Medical image analysis, AAA segmentation, Aorta segmentation

 


Farshid Faraji, MS
Assistant Specialist
farshid.faraji@ucsf.edu
Medical image analysis, Aortic disease, Intracranial aneurysms


Megan Ballweber, BS
Assistant Clinical Research Coordinator
megbee@gmail.com
Biomedical Imaging, Cardiovascular Disease


Collaborators

Diagnostic Radiology:

Neurology and Neurosurgery:

Cardiology, Vascular and Cardiovascular Surgery:

Neuro-Interventional Radiology:

Alumni

Featured Publications

Most Cited (> 40 citations)

  • Jou LD, Quick CM, Young WL, Lawton MT, Higashida R, Martin A, Saloner D. Computational approach to quantifying hemodynamic forces in giant cerebral aneurysms. AJNR Am J Neuroradiol. 2003 Oct;24(9):1804-10.
  • Markl M, Draney MT, Hope MD, Levin JM, Chan FP, Alley MT, Pelc NJ, Herfkens RJ.  Time-Resolved 3-Dimensional Velocity Mapping in the Thoracic Aorta: Visualization of 3-Directional Blood Flow Patterns in Healthy Volunteers and Patients. J Comput Assist Tomogr. 2004 Jul-Aug;28(4):459-468.
  • Hope MD, Meadows AK, Hope TA, Ordovas KG, Reddy GP, Alley MT, Higgins CB. Images in cardiovascular medicine. Evaluation of bicuspid aortic valve and aortic coarctation with 4D flow magnetic resonance imaging. Circulation. 2008 May 27;117(21):2818-9.
  • Boussel L, Rayz V, Martin A, Acevedo-Bolton G, Lawton MT, Higashida R, Smith WS, Young WL, Saloner D. Phase-contrast magnetic resonance imaging measurements in intracranial aneurysms in vivo of flow patterns, velocity fields, and wall shear stress: comparison with computational fluid dynamics. Magn Reson Med. 2009 Feb;61(2):409-17.
  • Boussel L, Arora S, Rapp J, Rutt B, Huston J, Parker D, Yuan C, Bassiouny H, Saloner D; MAPP Investigators. Atherosclerotic plaque progression in carotid arteries: monitoring with high-spatial-resolution MR imaging--multicenter trial. Radiology. 2009 Sep;252(3):789-96.
  • Hope MD, Meadows AK, Hope TA, Ordovas KG, Saloner D, Reddy GP, Alley MT, Higgins CB. Clinical Evaluation of Aortic Coarctation with 4D Flow MR Imaging. J Magn Reson Imaging. 2010 Mar;31(3):711-8.
  • Hope MD, Hope TA, Meadows AK, Ordovas KG, Urbania TH, Alley MT, Higgins CB. Bicuspid aortic valve: four-dimensional MR evaluation of ascending aortic systolic flow patterns. Radiology. 2010 Apr;255(1):53-61.
  • Hope MD, Hope TA, Crook SES, Ordovas KG, Urbania TH, Alley MT, Higgins CB. 4D Flow CMR in Assessment of Valve-Related Ascending Aortic Disease. JACC Cardiovasc Imaging. 2011 July;4(7):781-7.
  • Sughrue ME, Saloner D, Rayz VL, Lawton MT. Giant intracranial aneurysms: evolution of management in a contemporary surgical series. Neurosurgery. 2011 Dec;69(6):1261-70.
  • Hasan DM, Mahaney KB, Magnotta VA, Kung DK, Lawton MT, Hashimoto T, Winn HR, Saloner D, Martin A, Gahramanov S, Dósa E, Neuwelt E, Young WL. Macrophage imaging within human cerebral aneurysms wall using ferumoxytol-enhanced MRI: a pilot study. Arterioscler Thromb Vasc Biol. 2012 Apr;32(4):1032-8.
  • Markl M, Frydrychowicz A, Kozerke S, Hope M, Wieben O. 4D flow MRI. J Magn Reson Imaging. 2012 Nov;36(5):1015-36.

2015

  • Benedetti N, Hope MD. Prevalence and Significance of Incidentally Noted Dilation of the Ascending Aorta on Routine Chest CT in Older Patients. J Comput Assist Tomogr. J Comput Assist Tomogr. 2015 Jan-Feb;39(1):109-11. PMID: 25319605
  • Burris NS, Hope MD. Three-Directional Phase Contrast MRI Applications for Aortic Disease. MRI Clinics of North America. Magn Reson Imaging Clin N Am. 2015 Feb;23(1):15-23. PMID: 25476670
  • Sohrabi S, Hope M, Saloner D, Keedy A, Naeger D, Lorca MC, Ordovas KG. Left Atrial Transverse Diameter on Computed Tomography Angiography Can Accurately Diagnose Left Atrial Enlargement in Patients With Atrial Fibrillation. J Thorac Imaging. 2015 Jan 27. [Epub ahead of print] PMID: 25629578
  • Kari FA, Kocher N, Beyersdorf F, Tscheuschler A, Meffert P, Rylski B, Siepe M, Russe MF, Hope MD. Four-dimensional magnetic resonance imaging-derived ascending aortic flow eccentricity and flow compression are linked to aneurysm morphology. Interact Cardiovasc Thorac Surg. 2015 Jan 30. pii: ivu446. [Epub ahead of print] PMID: 25636325
  • Hope MD, Gasper WJ, Rapp J, Owens CD, Haraldsson H, Saloner D. Vascular Inflammation in a Growing Iliac Artery Aneurysm. Clin Nucl Med. 2015 Feb 11. [Epub ahead of print] PMID: 25674872
  • Sigovan M, Dyverfeldt P, Wrenn J, Tseng EE, Saloner D, Hope MD. Extended 3D Approach for Quantification of Abnormal Ascending Aortic Flow. Magn Reson Imaging. 2015 Feb 23. [Epub ahead of print] PMID: 25721998
  • Burris NS, Hope MD. Bicuspid Valve-Related Aortic Disease: Flow Assessment with Conventional Phase-Contrast MRI. Acad Radiol. 2015 Mar 10. [Epub ahead of print] PMID: 25769698
  • Saloner D, Liu J, Haraldsson H. MR physics in practice: how to optimize acquisition quality and time for cardiac MR imaging. Magn Reson Imaging Clin N Am. 2015 Feb;23(1):1-6.
  • Rayz VL, Abla A, Boussel L, Leach JR, Acevedo-Bolton G, Saloner D, Lawton MT. Computational modeling of flow-altering surgeries in basilar aneurysms. Ann Biomed Eng. 2015 May;43(5):1210-22.
  • Walker JP, Nosova E, Sigovan M, Rapp J, Grenon MS, Owens CD, Gasper WJ, Saloner DA. Ferumoxytol-enhanced magnetic resonance angiography is a feasible method for the clinical evaluation of lower extremity arterial disease. Ann Vasc Surg. 2015 Jan;29(1):63-8.
  • Burris NS, Johnson KM, Larson PE, Hope MD, Nagle SK, Behr SC, Hope TA. Detection of Small Pulmonary Nodules by Ultra-short Echo Time Sequences in Oncology Patients using a PET/MR System. Radiology. 2015 Jul 2:150489. [Epub ahead of print] PMID: 26133050
  • Hope MD, Hope TA, Zhu C, Faraji F, Heraldsson H, Ordovas KG, Saloner D. Vascular Imaging with Ferumoxytol as a Contrast Agent. AJR Am J Roentgenol. 2015 Jun 23:W1-W8. [Epub ahead of print] PMID: 26102308
  • Krishnan K, Ge L, Haraldsson H, Hope MD, Saloner DA, Guccione JM, Tseng EE. Ascending thoracic aortic aneurysm wall stress analysis using patient-specific finite element modeling of in vivo magnetic resonance imaging. Interact Cardiovasc Thorac Surg. 2015 Jul 14. pii: ivv186. [Epub ahead of print] PMID: 26180089
  • Dyverfeldt P, Bissell M, Barker AJ, Bolger AF, Carlhäll CJ, Ebbers T, Francios CJ, Frydrychowicz A, Geiger J, Giese D, Hope MD, Kilner PJ, Kozerke S, Myerson S, Neubauer S, Wieben O, Markl M. 4D flow cardiovascular magnetic resonance consensus statement. J Cardiovasc Magn Reson. 2015 Aug 10;17(1):72.
  • Nayak KS, Nielsen JF, Bernstein MA, Markl M, D Gatehouse P, M Botnar R, Saloner D, Lorenz C, Wen H, S Hu B, Epstein FH, N Oshinski J, Raman SV. Cardiovascular magnetic resonance phase contrast imaging. J Cardiovasc Magn Reson. 2015 Aug 9;17(1):71.
  • Zhang X, Zhu C, Peng W, Tian B, Chen L, Teng Z, Lu J, Sadat U, Saloner D, Liu Q. Scan-Rescan Reproducibility of High Resolution Magnetic Resonance Imaging of Atherosclerotic Plaque in the Middle Cerebral Artery. PLoS One. 2015 Aug 6;10(8):e0134913.

2014

  • Liu J, Saloner D. Accelerated MRI with CIRcular Cartesian UnderSampling (CIRCUS): a variable density Cartesian sampling strategy for compressed sensing and parallel imaging. Quant Imaging Med Surg. 2014 Feb;4(1):57-67.
  • Liu J, Nguyen TD, Zhu Y, Spincemaille P, Prince MR, Weinsaft JW, Saloner D, Wang Y. Self-gated free-breathing 3D coronary CINE imaging with simultaneous water and fat visualization. PLoS One. 2014 Feb 20;9(2):e89315.
  • Hope MD, Sigovan M, Wrenn SJ, Saloner D, Dyverfeldt P. Magnetic Resonance Imaging Hemodynamic Markers of Progressive Bicuspid Aortic Valve Related Aortic Disease. J Magn Reson Imaging. 2014 Jul;40(1):140-5. PMID: 24788592
  • Haraldsson H, Hope M, Acevedo-Bolton G, Tseng E, Zhong X, Epstein FH, Ge L, Saloner D. Feasibility of asymmetric stretch assessment in the ascending aortic wall with DENSE cardiovascular magnetic resonance. J Cardiovasc Magn Reson. 2014 Jan 9;16(1):6. PMID: 24400865
  • Burris NS, Sigovan M, Knauer HA, Tseng EE, Saloner D, Hope MD. Systolic Flow Displacement Correlates with Future Ascending Aortic Growth in Patients with Bicuspid Aortic Valves Undergoing MR Surveillance. Invest Radiol. 2014 Oct;49(10):635-9. PMID: 24784460
  • Liu J, Dyverfeldt P, Acevedo-Bolton G, Hope M, Saloner D. Highly Accelerated Aortic 4D Flow MR Imaging with Variable-Density Random Undersampling. Magn Reson Imaging. 2014 Oct;32(8):1012-20. PMID: 24846341
  • Thadani SR, Dyverfeldt P, Gin A, Chitsaz S, Rao RK, Hope MD. Comprehensive Evaluation of Culture-Negative Endocarditis with Use of Cardiac and 4-Dimensional-Flow Magnetic Resonance Imaging. Tex Heart Inst J. 2014 Jun 1;41(3):351-2. PMID: 24955064
  • Dusch MN, Thadani SR, Dhillon GS, Hope MD. Diastolic Function Assessed by Cardiac MRI Using Longitudinal Left Ventricular Fractional Shortening. Clin Imaging. 2014 Sep-Oct;38(5):666-8. PMID: 25034401
  • Velez E, Boyer N, Acevedo-Bolton G, Hope MD, Boyle A. CT-Reconstructed Three-Dimensional Printed Models of the Right Subclavian Artery and Aorta Define Age-Related Changes and Facilitate Benchtop Catheter Testing. J Invasive Cardiol. 2014 Oct;26(10):E141-4. PMID: 25274871
  • Hope MD, Sigovan M, Dyverfeldt P. Letter by hope et Al regarding article, "bicuspid aortic cusp fusion morphology alters aortic three-dimensional outflow patterns, wall shear stress, and expression of aortopathy". Circulation. 2014 Nov 4;130(19):e170. PMID: 25366842
  • Wisneski AD, Mookhoek A, Chitsaz S, Hope MD, Guccione JM, Ge L, Tseng EE. Patient-specific finite element analysis of ascending thoracic aortic aneurysm. J Heart Valve Dis. 2014 Nov;23(6):765-72. PMID: 25790625

Grants and Talks

Grants

  • RSNA #RF1502 “Combined Evaluation of Hemodynamic and Inflammatory Markers in Chronic Type B Aortic Dissection Using PET/MRI” (Burris, 2015)
  • 1R01HL123759-01A1 "Hemodynamic and inflammatory imaging in evaluation of abdominal aortic aneurysms" (Hope, 2015)
  • 1R01HL114118-01A1 "MRI of Structure and Function in Assessing Hemodynamic Impact on AAA Evolution" (Saloner, 2014)
  • 1K25EB014914-01A1 “4D MRI Development for Cardiovascular Imaging” (Liu, 2012)
  • RSNA #RSCH1215 “Comprehensive hemodynamic assessment of valve-related aortic disease with cardiac magnetic resonance” (Hope, 2012)
  • 1R01NS059944-01A2 "Determinants of Intracranial Aneurysm Growth" (Saloner, 2009)
  • 1R21CA123840-01A2 “Image-Guided Monitoring of Meningioma Embolization in a Combined MRI/XRA Suite” (Saloner, 2007)

2015 Talks

MRA Club 2015, 27th Annual International Conference, Cincinnati:

  • Turbulence tensor quantification using ICOSA6 flow encoding (Haraldsson)
  • Application of Full Turbulent Tensor in Estimation of MR-Based Relative Pressure (Kefayati)
  • Assessment of tortuosity and flow in abdominal aortic aneurysms with ferumoxytol-enhanced magnetic resonance imaging (Faraji)
  • Ferumoxytol MRA as an Alternative to CTA for Common Chest Indications: TAVR and Pulmonary Embolism (Hope)
  • High resolution MRI for characterization of inflammation within abdominal aortic aneurysm (Zhu)
  • Intracranial Vessel Wall Imaging at 3T and 7T (Saloner)

3rd Oxford 4D Flow Workshop, 2015, Oxford, UK:

  • “Clinical Utility of 4D Flow MRI: How, Where and Why? -- Aorta” (Hope)

International Society for Computed Tomography (ISCT) 2015, San Francisco:

  • “Noncontrast CT: Is it really needed for acute aortic evaluation?”
  • “Penetrating Aortic Ulcer versus Pseudoaneurysm: Where is the line?”
  • “Post-Operative Aorta: What’s normal and what’s a catastrophe” (Hope)

 

 Research Projects

Abdominal Aortic Aneurysms

  • 1R01HL123759-01A1 "Hemodynamic and inflammatory imaging in evaluation of abdominal aortic aneurysms" (Hope, 2015)
  • 1R01HL114118-01A1 "MRI of Structure and Function in Assessing Hemodynamic Impact on AAA Evolution" (Saloner, 2014)

Goal: To elucidate the mechanisms of growth and rupture of small abdominal aortic aneurysms (AAAs) with a combined hemodynamic and inflammatory assessment using functional aortic imaging techniques.

Motivation: Abdominal aortic aneurysms (AAA) are common and can be life-threatening if they progress to rupture. They have been reported in 5% of older men and account for over 15,000 deaths per year. Basic vVessel dimensions are currently the primary imaging measurement clinically used clinically to risk-stratify patients. But there is more to the story than dimensions. Wall stress estimated with computational modeling may better predict growth and rupture than diameters. Growth is often not continuous, and instead marked by periods of rapid growth followed by quiescence. Small series report that unrelated surgical procedures can precipitate AAA rupture. These findings suggest that episodic and heterogeneous inflammatory processes in concert with adverse hemodynamics are important for the progression of AAA disease.

Rationale: The complexity of aortic disease is more fully revealed with new functional imaging techniques than with conventional anatomic analysis alone. While AAA has been extensively studied, the mechanisms of disease progression have not been fully elucidated. If better understood, the management of patients with small AAAs (< 5.5cm) could be significantly improved. Many of these aneurysms can be followed safely with a long screening interval of 2-3 years, but some may progress to rupture. Identifying this subset would greatly streamline the surveillance imaging of the millions of patients with AAA. On the other hand, the majority of AAAs never rupture, and identifying low risk patients could help better manage resources and subject only those patients at truly elevated risk to intervention.

We hypothesize that the systemic inflammation experienced with unrelated surgery will lead to AAA growth, and that this growth will occur at sites of unfavorable hemodynamics. Revealing such a combined inflammatory and hemodynamic mechanism for progression of AAA disease would constitute a substantial advancement in knowledge that would have both direct and broad clinical implications.

Strategy: Aortic wall inflammation can be evaluated with the MRI contrast agent ferumoxytol, which has macrophage-selective properties on delayed imaging. MRI also offers a unique and comprehensive assessment of aortic hemodynamics. Blood flow imaging with 3D time-resolved, 3D phase- contrast MRI (4D Flow) allows quantification of key secondary vascular parameters including turbulence and wall shear stress (WSS). Cine Displacement Encoding with Stimulated Echos (DENSE) can quantify regional stretch differences experienced by the vessel wall. Computational modeling based on MRI volumetric data can be used to calculate wall stress. We propose that analysis of these hemodynamic parameters along with transient inflammation will be central to understanding the progression of AAA disease., we have found an excellent and clinically relevant disease process for demonstrating the potential of 4D Flow in the management of patients with cardiovascular disease.

We intend to study patients with small AAAs before and after unrelated surgery with a combined inflammatory and hemodynamic assessment, and follow their progress with regular surveillance imaging.

Expected Outcome and Impact: The goal of our study is to uncover important inflammatory changes and adverse hemodynamics that are not addressed with current imaging, and use them to predict disease progression. Our approach is unique both in our targeting of patients undergoing unrelated surgery and our comprehensive use of new functional imaging techniques. We seek to meaningfully advance the assessment of risk in patients who do not meet current intervention thresholds and improve outcomes by refining surveillance imaging regimens and decisions regarding early intervention for AAAs.

Intracranial Aneurysms

  • 1R01NS059944-01A2 "Determinants of Intracranial Aneurysm Growth" (Saloner, 2009)

Accelerated 4D MRI

  • 1K25EB014914-01A1 “4D MRI Development for Cardiovascular Imaging” (Liu, 2012)

Assessments of coronary artery disease and ventricular function are crucial elements for heart health evaluation. The goal of this research is to develop 4D magnetic resonance imaging (MRI) techniques that provide a non-invasive and effective cardiac imaging examination, including assessing coronary artery disease (CAD) and both left (LV) and right ventricular (RV) function. 

Echocardiography (ECHO) is widely used to assess function but is limited to 2D views of the anatomy. It has poor ability to measure RV dimensions given the position, trabeculations, and complex anatomy of the RV. CT angiography (CTA) provides non-invasive assessment of CAD and ventricular function, however it involves exposure to ionizing radiation and risk of nephrotoxicity from iodinated contrast agents. Adequate CTA generally requires the use of beta blockers and is improved by the administration of nitroglycerin, both of which are contraindicated for certain patients. Coronary angiography (CA) is the definitive study for identifying the presence of CAD, but it is invasive, costly in both dollar terms and patient morbidity, and provides no assessment of ventricular function. 

Cardiac magnetic resonance imaging (MRI) offers several powerful capabilities. It is the gold standard for quantitating ventricular function with 2D breath-hold cine acquisitions. Whole-heart coronary MRA centered on mid-diastole has also been demonstrated without contrast injection. However, both applications are limited by the challenges posed by cardiac and breathing motion. Cardiac function quantitation on 2D MRI suffers from breathing inconsistencies and consequent slice-to-slice spatial misregistration, particularly when patients, such as lung transplantation candidates, are unable to perform even a short breath-hold. Inconsistent breathing and selection of a fixed window at mid-diastole results in unacceptable scan times and reduces image quality in coronary studies since some coronary segments are not quiescent at that time. 

In this research we aim to: 1) develop self-gated free-breathing 4D cardiac MRI with novel self-gating, motion correction, and advanced image reconstruction methods;2) optimize a 4D MRI protocol for cardiac function imaging and coronary artery imaging;and 3) implement the optimized methods in assessment of cardiac patients. Successful implementation of the proposed 4D cardiac MRI will not only be important for assessing CAD and ventricular function, but will be generalizable to conditions requiring similar capabilities, such as evaluation of valve disease, enhanced imaging of ischemic myocardium and assessment of vascular compliance. This will offer improved care for the vast population of patients with these conditions and financial benefits for the healthcare system.

Aortic Dissection

  • RSNA #RF1502 “Combined Evaluation of Hemodynamic and Inflammatory Markers in Chronic Type B Aortic Dissection Using PET/MRI” (Burris, 2015)

The purpose of this study is to investigate the role of vessel wall inflammation and hemodynamic alterations in progressive enlargement of chronic type B aortic dissections.  Using the novel hybrid imaging technology Positron Emission Tomography-Magnetic Resonance Imaging (PET/MRI), we seek to develop and optimize a non-invasive imaging protocol for the concurrent evaluation of anatomy, inflammation, and hemodynamics within an individual patient. Vessel wall inflammation will be evaluated using macrophage-selective (“cellular”) imaging contrast agent (ferumoxytol) in addition to a standard (“metabolic”) inflammatory imaging agent, fluorodeoxyglucose-PET (FDG-PET). Hemodynamic evaluation will be accomplished using time-resolved three-dimensional phase-contrast MRI (4D Flow), a comprehensive flow imaging technique. Using this combined imaging approach we seek to identify relations among metabolic and cellular inflammation, hemodynamics, and progressive aortic enlargement.

Significance of health problem:
Aortic dissection is a life-threatening cardiovascular event initiated by tearing of the aortic intima, the “entry tear”. This allows high-pressure pulsatile blood to travel within the aortic wall, between the intimal and medial layers, often leading to compression of the true aortic lumen and its principal branches. Risk and timing of mortality depend on the segment of the thoracic aorta that is involved.1 Type A dissections, which involve the ascending aorta or arch, kill acutely and require timely surgical intervention. Mortality is approximately 1% per hour that surgical repair is delayed within the first day.2 In comparison, type B dissections are limited to the descending aorta, are usually managed medically (73% of cases), and have a lower acute mortality rate (~10%) compared to type A (~30%).3,4

Despite lower acute mortality rates of type B dissections, as compared to type A dissections, long-term outcomes of patients with type B dissections are unpredictable with substantially higher mortality at follow-up. Among patients with aortic dissection who survive to hospital discharge, those with type B have a higher 3-year mortality rate at follow-up (25%), compared to patients with surgically repaired type A dissection (10%).5 Additionally, those with type B dissection who do require surgical intervention also experience high operative mortality rates (30%).6 Minimally invasive approaches, such as endovascular stent grafting (TEVAR), have reduced both operative and long-term morbidity and mortality associated with type B dissection.7-9 However, progression of type B dissection is heterogeneous and many patients with type B dissections do not require surgical intervention, remaining stable at follow-up with medical therapy alone (~60% at 5 years).10 Currently, there is no accurate way to predict which patients will remain stable versus those who will progress and are most likely to benefit most from surgical intervention over conservative management.

Current therapy and limitations:
The current standard of care for all stages of type B dissection (acute, sub-acute, and chronic) is treatment with anti-hypertensive medications.11 Anti-hypertensive therapy is aimed at reducing pressure within a patent false lumen, the presence of which has been found to increase the risk of progressive disease.12 If the false lumen remains patent and exposed to aortic pressure, it will progressively enlarge in the vast majority of cases (84%) despite blood pressure management.12,13 As such, long-term mortality with medical therapy alone remains unacceptably high, at approximately 30% at 5 years.7

Surgical treatment of type B dissection is indicated when anatomic threshold are reached, such as rapid expansion or aneurysmal dilation of the dissected segment of aorta (maximal diameter >5.5 cm or annual growth rate >4 mm/year).11 Traditional “open” surgical repair of type B dissection is a highly invasive procedure associated with high in-hospital mortality (~30%).6 TEVAR is a recent and increasingly popular endovascular approach to treating type B dissection and has greatly reduced operative mortality, although it is currently used in less than 30% of surgical cases.9 In TEVAR, a stent graft is used to occlude the entry tear thereby promoting thrombosis of the false lumen and accelerating vascular remodeling.14 Recent studies of TEVAR have also found reduced long-term mortality among patients with chronic type B dissections (15.5% versus 29.0% with standard medical management).7 TEVAR is a promising treatment for type B dissection; however, targeting this intervention to patients with greater risk for progressive enlargement may further improve patient outcomes.

There is currently no reliable strategy to accurately predict if a patient with chronic type B dissection will remain stable or develop future complications. Current guidelines for chronic type B dissection intervention are based on a “watch and wait” surveillance approach using simple anatomic thresholds obtained from surveillance CT or MRA examinations.11 Other factors that drive aortic growth (e.g. hemodynamics, inflammatory wall remodeling) are largely ignored by this anatomic approach, but could be imaged non-invasively by PET/MRI.15-17 Consideration of these additional factors may improve individual risk assessment, allowing for more targeted and effective intervention in this challenging group of patients. A combined PET/MRI protocol that simultaneously assesses both anatomic and novel functional parameters may increase understanding of the pathophysiology underlying type B dissection, and promote discovery of new treatment strategies.

The role of inflammation:
Inflammation is an important risk factor for cardiovascular disease.18-20 While there is limited understanding of the role of inflammation in type B dissection, its role in the progression of abdominal aortic aneurysm (AAA), a related disease, is well documented.21 Dissection and AAA have similar pathophysiology; both involve inflammation, extracellular matrix remodeling, medial degeneration, and abnormal hemodynamic stresses leading to aneurysmal dilation or rupture.22 In AAA, lymphocytes and macrophages stimulate production of proteolytic enzymes, which participate in extracellular matrix disruption, smooth muscle necrosis, and aortic wall weakening.21,23,24 In dissection, inflammation has been investigated as a contributor to adverse outcomes.22 At the vessel wall level, lymphocytes and macrophages concentrate around areas of smooth muscle necrosis, suggesting an association between inflammatory cell infiltration and aortic wall weakening and disruption.25

Non-invasive imaging techniques have made assessment of vessel wall inflammation possible for surveillance of patients with chronic type B dissection. FDG-PET imaging assesses the general metabolic activity of non-specific inflammation. FDG uptake at the site of aortic pathology is associated with increased growth rate and risk of rupture in dissection and AAA patients. 15,26-28 Recent development of a macrophage-specific MRI contrast agent, ferumoxytol, has made evaluation of local cellular inflammation possible.29 Ferumoxytol is an ultrasmall superparamagnetic iron oxide (USPIO), and can be used as a MRI contrast agent for magnetic resonance angiography (MRA). When imaged 2-4 days after injection, ferumoxytol localizes to macrophages and can be visualized by MRI as areas of signal loss due to iron-related susceptibility artifact.30-32 Detection of ferumoxytol in the wall of AAAs at delayed imaging has been correlated with accelerated aneurysm growth.17 Given the physiologic similarities between AAA and dissection, ferumoxytol imaging may elucidate mechanisms of growth in type B dissection. While both are promising imaging markers of progressive disease, FDG-PET and ferumoxytol image inflammation in different ways, and it remains unclear what their respective associations are with aortic growth.

The role of hemodynamics:
Despite adequately managed blood pressure, aortic flow remains distinctly abnormal in type B dissection patients. Pressurized flow within the false lumen adds hemodynamic stress to the intrinsically weak wall of the false lumen. Partial thrombosis is hypothesized to restrict false lumen outflow, elevating false lumen pressures, and increasing risk of mortality.13 Several abnormal flow patterns have been described in type B dissection including: high velocity jets at the site of entry tear, eccentric helical flow, and slow multidirectional flow in the false lumen.16,33 These patterns can be visualized and quantified with an advanced flow imaging technique, time-resolved three-dimensional phase contrast MRI (4D Flow).16 Our group has substantial experience using this technique to assess aortic disease.34-37 A recent 4D Flow study reported that flow eccentricity and peak velocity are associated with increased rate of false lumen expansion.16 However, the association of hemodynamic factors with inflammatory markers has not been investigated.

How this proposal addresses the problem:
This proposal targets the identification of functional predictors of disease progression not captured by the current anatomic approach to imaging surveillance. PET/MRI technology streamlines the concurrent assessment of non-specific inflammation (FDG-PET), cellular inflammation (ferumoxytol), hemodynamics (4D Flow), and gold standard anatomic measurements (MRA). A combined imaging approach to identify important hemodynamic and inflammatory abnormalities early in disease may help target intervention to patients at highest risk for complications, before they develop. Until risk stratification methods incorporate parameters beyond anatomic measurements, the opportunity to improve treatment of chronic type B dissection is limited, and long-term outcomes are likely to remain suboptimal.