4D Flow Applications to Interventional Radiology

In 1960, magnetic resonance imaging (MRI) characterized flow velocities of sea water with a precision of 10-8 centimeters per second(1). When applied to human blood, flow-sensitive MRI can detect a variety of flow properties characteristic of pathological change.

Flow-sensitive MRI protocols have recently evolved from “2D phase contrast” to “4D flow.” 2D phase contrast had the capability to characterize through-plane or in-plane flow measurements, secondary to one-way velocity encoding. 4D flow, however, can characterize flow properties within a 3D volumetric region, secondary to three-way velocity encoding. 4D flow images can be interrogated with a posteriori analyses and yield detailed information, such as vorticity(2), wall shear stress (WSS)(3), and turbulent kinetic energy(4).

Through applying 4D flow imaging, interventional radiologists may be able to improve the efficacy of their neurovascular, lymphatic, and hepatic interventions.

Pathology related to the neuro-vasculature often presents in high acuity settings. It would be valuable if aneurysm rupture or progression could be predicted by 4D flow-derived measurements, such as WSS. Several studies have already shown that correlations exist between intra-aneurysmal flow and WSS with aneurysm characteristics.

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Arteriovenous malformations (AVMs) represent another opportunity for pre-intervention imaging. It has been suggested that quantitative 4D flow can identify AVM tributary arteries with the highest flow rates. This may enable more successful targeted-embolization treatment of AVMs, prior to surgical resection(5).

4D flow also has potential application, after neurovascular interventions. Flow-diverter stents are currently used to treat sidewall intracranial aneurysms. Despite low velocities within these stents, a flow change index (proportional velocity reduction ratio) was contrived(6). Indices, such as this imply potential for the clinical implementation of 4D flow MRI in post-procedure monitoring, despite metallic stents and low-flow properties in this setting.

Properties of lymph fluid (few cells, clear fluid) and the lymph system itself (variable presence of fluid within vessels) present challenges for visualization. Although procedures, such as thoracic duct and intrahepatic lymphatic duct embolization have been reported, imaging challenges limit the role of the interventionalist in patients with lymphatic disorders.

Lymphatic vessels lie deep, below superficial lymphatic networks, and actively contract via unknown mechanisms. Because 4D flow can quantify flow patterns in volumetric regions of interest, it may hold value in better understanding the interrelatedness of venous, arterial, and lymphatic flows as they relate to disease. Several animal studies have investigated ways that lymph flow relates to tissue pressures(7,8). Dynamic 4D contrast-enhanced magnetic resonance lymphangiography has been shown to demonstrate the time course of contrast agent flow up the central lymphatic ducts(9) and doppler optical coherence tomography has been shown to depict lymph velocity at high temporal resolution(10). 4D flow may enhance our understanding (and visualization) of the lymphatic system.

Portal blood flow has also been studied with 4D flow MRI. Flow volumes were shown to significantly increase in the superior mesenteric vein and portal vein (PV) after transjugular intrahepatic portosystemic shunt (TIPS) placement. In this same cohort, flow differences were seen in the TIPS to PV flow ratio between the six patients with resolved ascites at two and 12 weeks after TIPS (0.8 and 0.9, respectively) and the one patient with refractory ascites (4.6 and 4.2, respectively)(11). Patency and stenosis evaluation following TIPS placement(12)and following PV stent placement(13) represent additional opportunities for 4D flow analysis of the portal vasculature.

In conclusion, 4D flow MRI provides clinicians with advanced quantifiable measures of blood flow. Although the technology is in its early stages, and more applications are being realized, post- and pre- intervention 4D flow acquisitions appear capable of providing clinicians with valuable insight. Pre-procedural 4D flow MRI may improve understanding (and disease screening) in the vascular and lymphatic systems. Post-procedural monitoring similarly appears to be a useful application of 4D flow MRI, especially in the neuro- and portal- vasculature.

According to Charles Dotter, M.D., “If a plumber can do it to pipes, we can do it to blood vessels”. Rerouting and restoring blood flow is the concept behind much of an interventional radiologist’s work. Delicate blood vessels, however, are not steel pipes. If we can better understand blood flow, we can better treat patients. Instead of simply sea(ing) water move, we can now “sea” blood move. Let’s make the most of this remarkable ability and continue to push interventional radiology forward.

Follow Editorial Board member Jack Cerne, M.D., on Twitter @JackCerne.

References

1. Hahn EL. Detection of sea-water motion by nuclear precession. J Geophys Res 1896-1977. 1960;65(2):776–7.

2. Schäfer M, Humphries S, Stenmark KR, Kheyfets VO, Buckner JK, Hunter KS, et al. 4D-flow cardiac magnetic resonance-derived vorticity is sensitive marker of left ventricular diastolic dysfunction in patients with mild-to-moderate chronic obstructive pulmonary disease. Eur Heart J Cardiovasc Imaging. 2018 Apr 1;19(4):415–24.

3. Szajer J, Ho-Shon K. A comparison of 4D flow MRI-derived wall shear stress with computational fluid dynamics methods for intracranial aneurysms and carotid bifurcations - A review. Magn Reson Imaging. 2018 May;48:62–9.

4. Binter C, Gotschy A, Sündermann SH, Frank M, Tanner FC, Lüscher TF, et al. Turbulent Kinetic Energy Assessed by Multipoint 4-Dimensional Flow Magnetic Resonance Imaging Provides Additional Information Relative to Echocardiography for the Determination of Aortic Stenosis Severity. Circ Cardiovasc Imaging. 2017 Jun;10(6):e005486.

5. Schnell S, Wu C, Ansari SA. 4D MRI flow examinations in cerebral and extracerebral vessels. Ready for clinical routine? Curr Opin Neurol. 2016 Aug;29(4):419–28.

6. Pereira VM, Brina O, Delattre BMA, Ouared R, Bouillot P, Erceg G, et al. Assessment of intra-aneurysmal flow modification after flow diverter stent placement with four-dimensional flow MRI: a feasibility study. J NeuroInterventional Surg. 2015 Dec 1;7(12):913–9.

7. Swartz MA, Kaipainen A, Netti PA, Brekken C, Boucher Y, Grodzinsky AJ, et al. Mechanics of interstitial-lymphatic fluid transport: theoretical foundation and experimental validation. J Biomech. 1999 Dec;32(12):1297–307.

8. Leu AJ, Berk DA, Lymboussaki A, Alitalo K, Jain RK. Absence of functional lymphatics within a murine sarcoma: a molecular and functional evaluation. Cancer Res. 2000 Aug 15;60(16):4324–7.

9. Dori Y, Zviman MM, Itkin M. Dynamic Contrast-enhanced MR Lymphangiography: Feasibility Study in Swine. Radiology. 2014 Nov 1;273(2):410–6.

10. Blatter C, Meijer EFJ, Nam AS, Jones D, Bouma BE, Padera TP, et al. In vivo label-free measurement of lymph flow velocity and volumetric flow rates using Doppler optical coherence tomography. Sci Rep. 2016 Jul 5;6(1):29035.

11. Bannas P, Roldán-Alzate A, Johnson KM, Woods MA, Ozkan O, Motosugi U, et al. Longitudinal Monitoring of Hepatic Blood Flow before and after TIPSby Using 4D-Flow MR Imaging. Radiology. 2016 Nov 1;281(2):574–82.

12. Owen JW, Saad NE, Foster G, Fowler KJ. The Feasibility of Using Volumetric Phase-Contrast MR Imaging (4D Flow) to Assess for Transjugular Intrahepatic Portosystemic Shunt Dysfunction. J Vasc Interv Radiol. 2018 Dec 1;29(12):1717–24.

13. Hyodo R, Takehara Y, Mizuno T, Ichikawa K, Ogura Y, Naganawa S. Portal Vein Stenosis Following Liver Transplantation Hemodynamically Assessed with 4D-flow MRI before and after Portal Vein Stenting. Magn Reson Med Sci. 2020;advpub.