Keywords
genicular artery embolization - osteoarthritis - angiographic anatomy
Introduction
Genicular artery embolization (GAE) is a novel, minimally invasive therapy for patients
with mild to moderate osteoarthritic (OA) knee pain.[1] Initially described for hemarthrosis,[2]
[3] GAE for OA pain has shown promising 4-year follow-up results from its initial investigations.[4]
[5]
[6] Because of the encouraging initial results, further prospective and randomized-controlled
trials are currently underway in the United States, Japan, and the United Kingdom.
In the majority of patients with knee OA, the articular cartilage breakdown is associated
with chronic synovitis.[7] This inflammatory process results in the formation of new blood vessels and subsequent
recruitment of new sensory nerve fibers within the synovium, resulting in chronic
knee pain.[8]
[9] The goals of embolizing the neovascularity are twofold: cause ischemic neurolysis
of the synovial sensory nerves and disrupt the inflammatory positive feedback cycle,
ultimately resulting in decreased pain and disability.[6]
[10]
[11]
[12]
[13]
The success of GAE, as well as the prevention of nontarget embolization, is related
to an in-depth understanding of the genicular arterial anatomy. Several studies[14]
[15]
[16] have addressed this topic using cadavers, but an angiographic analysis is yet to
be reported. The present study describes genicular angiographic findings, proposes
an angiographic classification, and discusses implications of genicular arterial variations
for the GAE procedure.
Materials and Methods
The study was approved by the local institutional review board and all study activities
followed the Health Insurance Portability and Accountability Act regulations.
Angiographic findings from 41 GAE procedures performed in 40 subjects to treat OA
pain from January 2017 to July 2019 were reviewed. Angiograms from two procedures
were unable to be analyzed due to technical reasons and were excluded from the study
for a total of 38 patients and 39 procedures. At baseline, all patients had clinical
(pain at least 5 on a scale of 10) and radiographic evidence of knee osteoarthritis
(Kellgren-Lawrence Grade 1–3 severity). Response to therapy was assessed with the
Western Ontario McMaster Universities Osteoarthritis Index and a Visual Analog Scale
for pain. Additionally, incidence and severity of adverse events were evaluated at
baseline, 1-, 3-, and 6-month follow-up. Clinical results from one of the two clinical
studies has been published previously.[17]
Procedures were performed according to previously described techniques.[5]
[6]
[17] Under moderate sedation, arterial access was obtained through the contralateral
femoral artery with a 6F sheath. Subsequent lower-extremity digital subtraction angiography
was performed from the distal femoral artery to capture the complete genicular arterial
anatomy between the origins of the descending genicular artery (DGA) and anterior
tibial recurrent artery (ATRA). A 2.4F microcatheter (Terumo, Princeton NJ, or Boston
Scientific, Natick, Massachusetts) was used to catheterize specific genicular arteries
and deliver 75–300 um spherical particles (Embozene: Boston Scientific, Natick, Massachusetts;
or Optisphere: Medtronic, Minneapolis, MN) to hypervascular regions consistent with
areas of pain.
Three interventional radiologists with experience (7–9 years) performing embolizations
analyzed all arteriograms and studied the following vessels: DGA, medial superior
genicular artery (MSGA), medial inferior genicular artery (MIGA), lateral superior
genicular artery (LSGA), lateral inferior genicular artery (LIGA), and ATRA. The presence
of the arteries, diameter within 1 cm of their origin, branching pattern, angle of
origin to the proximal parent vessel, anastomotic network, and distance from the origin
of the DGA were recorded for each vessel. Additional measurements included popliteal
diameter 1 cm below the DGA origin and radiation dosage. The average fluoroscopy time
was compared between patients with all vessels present (M1 or L1) and patients with
at least one vessel missing (M2 or L2) to evaluate the effects of anatomical variations
on overall procedural time and radiation dose.
The branching patterns were classified into following subtypes:
-
Medially:
-
M1 (presence of all three medial branches: DGA, MSGA, MIGA).
-
M2 (presence of two of the three medial branches: either DGA and MSGA or DGA and MIGA).
-
Laterally:
-
L1 (presence of all three lateral branches: LSGA, LIGA, ATRA).
-
L2 (presence of two of the three lateral branches: either ATRA and LSGA or ATRA and
LIGA).
Results
[Fig. 1(A–F)] identifies the six main arteries being studied. Of the 108 total arteries selected,
91 were treated: DGA (24/91, 26.4%), MIGA (21/91, 23.1%), MSGA (20/91, 22.0%), LIGA
(13/91, 14.3%), and LSGA/ATRA (13/91, 14.3%). The difference in selected vs embolized
arteries refers to catheterized vessels in the region of pain that were negative for
hypervascularity and therefore did not receive treatment. The following branching
patterns were observed—medially: M1 = 74.4% (n = 29/39), M2 = 25.6% (n = 10/39); laterally: L1 = 94.9% (n = 37/39), L2 = 5.1% (n = 2/39). The M1 and L1 branching pattern was seen in 27 procedures and the M2 or
L2 branching pattern was seen in 12 procedures. A common origin for MSGA and LSGA
was noted in 11 out of 39 procedures (28.2%). Additional analysis of the DGA branching
pattern revealed direct DGA origin from the popliteal artery in 3 out of 39 procedures
(7.7%, n = 3). The procedure was performed bilaterally on one patient and right vs left knee
analysis revealed a M1L1 branching pattern on both sides, but a common origin for
the MSGA and LSGA was noted on the right side.
Fig. 1 Overview of the genicular arteries: (A) descending genicular artery (DGA); (B) medial superior genicular artery; (C) medial inferior genicular artery; (D) lateral superior genicular artery; (E) lateral inferior genicular artery; (F) anterior tibial recurrent artery; (G) saphenous branch of DGA; (H) musculoarticular branch of DGA.
[Table 1] summarizes the frequency, diameter, angle of origin, and distance from DGA for all
six arteries. Anastomotic supply to another genicular artery in selected vessels was
recorded (26.4%, 24/91). Anastomotic relationships were noted between DGA and MSGA/LSGA,
MIGA and LIGA, and LSGA and LIGA/ATRA. The average popliteal diameter was 7.55 ± 1.54
mm and the average administered reference air kerma level was 128.31 ± 106.21. No
significant difference was noted when comparing mean fluoroscopy time, in minutes,
of M1 or L1 (n = 27) vs M2 or L2 (n = 12): 27.47 ± 13.8 vs 20.47 ± 5.56; p = 0.10.
Table 1
Summary of genicular artery measurements
|
Artery
|
Frequency
|
Diameter
|
Angle (<90)
|
Distance
|
|
Abbreviations: ATRA, anterior tibial recurrent artery; DGA, descending genicular artery;
LIGA, lateral inferior genicular artery; LSGA, lateral superior genicular artery;
MIGA, medial inferior genicular artery; MSGA, medial superior genicular artery, NA,
not available.
Note: All distance and diameter measures (mm) are summarized as mean values along
with the respective standard deviations. The angle of the selected vessel was compared
to the proximal parent artery (e.g., popliteal artery).
|
|
DGA
|
39/39 100.0%
|
2.4
|
5.4%
|
NA
|
|
0.8
|
NA
|
|
MSGA
|
33/39 84.6%
|
1.2
|
97.1%
|
10.6
|
|
0.5
|
3.6
|
|
MIGA
|
35/39 89.7%
|
1.6
|
8.8%
|
17.3
|
|
0.5
|
4.4
|
|
LSGA
|
38/39 97.4%
|
1.5
|
94.6%
|
11.6
|
|
0.4
|
4.0
|
|
LIGA
|
38/39 97.4%
|
1.5
|
71.4%
|
18.7
|
|
0.4
|
4.9
|
|
ATRA
|
39/39 100.0%
|
1.6
|
100.0%
|
25.7
|
|
0.5
|
4.6
|
Discussion
Classification
Knee pain in osteoarthritis can generally be lateralized to either the medial or lateral
aspect of the knee. The first step in GAE involves mapping the vasculature associated
with the corresponding painful region of the knee. Cadaveric studies have previously
reported variations in genicular arterial anatomy and proposed two different classification
patterns.[18]
[19] The classification types mainly involve differences in the middle genicular artery
(MGA) branching pattern and its common origin with other genicular arteries. The MGA
was not treated in the present study given its limited perfusion of the knee. The
purpose of the current classification system is to create a clinically oriented model
that could be used for consistent reporting in future GAE studies. Additionally, the
classification system could help predict the overall procedural time and give information
about the complexity of anastomotic networks.
Medial Compartment
The medial compartment of the knee is perfused by the DGA, MSGA, and MIGA. The DGA
originates from the distal superficial femoral artery (SFA) and has an inverted “Y”
appearance. It divides into a straight medial saphenous branch, which courses superficially,
and a more torturous lateral musculoarticular branch, which courses deeper in the
knee. The DGA was present in all patients in this analysis. Anatomical studies have
reported variations in DGA anatomy with isolated origins of the DGA branches from
the distal SFA.[20] Although similar variations were not present in the current study, the DGA originated
in three patients from the above-knee popliteal artery instead of the distal SFA.
The MSGA was the most commonly absent of the medial genicular arteries (present 84.6%
of the time) and had the smallest mean diameter (1.2 mm). In some patients, the MSGA
was less than 1 mm and could not be catheterized. It is important to adequately evaluate
for collateral pathways of perfusion in patients with a very small or absent MSGA,
performing high-quality angiography of both the MIGA and DGA.
The MIGA originates from the popliteal artery near the joint space and descends along
the upper margin of the popliteus, before coursing anteriorly and superiorly creating
the angiographic “V” around the medial tibial metaphysis. The MIGA was absent in four
patients and should be distinguished from the adjacent sural arteries, which follow
a straight downward course toward the musculature.
Lateral Compartment
The lateral compartment is perfused by the LSGA, LIGA, and ATRA. Compared to the medial
compartment, less variation was noted in the lateral vasculature. The LSGA originates
from the popliteal artery at the level of the lateral femoral condyle and splits into
the superficial and deep branches. The LIGA originates around the joint space and
courses laterally above the fibular head before wrapping around the lateral tibial
condyle, creating a “J” appearance. The LSGA and LIGA were rarely absent but a common
origin of the MSGA and LSGA was noted in 11 patients (28.2%). Although the MGA was
not analyzed in the present study, anatomical studies have previously reported common
branching between MSGA, LSGA, and MGA.[21]
[22] This common trunk may make catheterization of each target vessel more challenging,
especially given its frequent acute angle of origin.
The ATRA is the most inferior branch supplying the knee and originates from the anterior
tibial artery just proximal to its origin. The ATRA was present in all patients with
an acute angle of origin relative to the anterior tibial artery.
Anastomotic Networks
Anastomoses between genicular arteries were often observed when injecting a specific
genicular artery during angiography (26.4%, 24/91). Observation of anastomoses was
highest in cases with variant anatomy (M2 and L2). The most common anastomosis was
noted between the musculoarticular branch of the DGA and the MSGA/LSGA ([Fig. 2]). This relationship can be explained given that the MSGA is the most commonly absent
vessel and had the smallest diameter of all six vessels. Similar pathways were observed
between other genicular branches, highlighting the need to explore all three vessels
on the symptomatic side for anastomosis and variant anatomy. Although selecting all
vessels can increase the fluoroscopy time, significant difference in fluoroscopy time
was not observed while comparing M1/L1 vs M2/L2.
Fig. 2 The medial superior genicular artery (MSGA) (A) is selected and anastomoses between the MSGA and the musculoarticular branch of
the descending genicular artery (B) is visualized.
Challenges
One of the major challenges in GAE is correctly identifying and navigating the vascular
anatomy, particularly the angle of origin. The angle of origin can prolong catheterization
time, fluoroscopy time, and has implications for proper catheter selection. The angle
of origin in most vessels was obtuse relative to the proximal popliteal artery, providing
an easier angle to catheterize, and thereby allowing the use of nonshaped microcatheters.
The MSGA/LSGA/ATRA are difficult arteries to catheterize given the acute angle of
origin relative to the popliteal artery ([Fig. 3]). Wires with longer length and flexible tips may not provide enough support to advance
the microcatheter, and preshaped microcatheters can offer an advantage. The operators
in this study used a variety of wire and microcatheter combinations at their discretion.
Fig. 3 The acute angle of origin of the medial superior genicular artery relative to the
proximal popliteal artery is demonstrated.
Another major challenge to GAE is preventing nontarget embolization. Cutaneous arteries
may be confused for genicular synovial branches leading to multiple side-effects.
Cutaneous arteries appear perpendicular to the main genicular arteries extending to
the cutaneous surface, and embolizing proximal to these vessels may lead to cutaneous
ischemia. Although most often reported as subclinical and self-resolving, the possibility
of ulceration is present. The presence of a common origin, especially of MSGA/LSGA,
is an important consideration, as reflux could lead to nontarget embolization to the
asymptomatic side. Similarly, collateral networks can cross the joint space and anastomose
with ipsilateral and contralateral vessels. Recognizing the typical anatomy and anticipating
for variants are vital for best patient outcomes and minimizing risk.
Conclusion
The knee joint has a complex vascular network with extensive anastomotic networks
and anatomical variations. During GAE, a thorough understanding of the genicular artery
anatomy is important for maximizing clinical outcomes for pain reduction while minimizing
complications, procedure time, and radiation exposure. As experience increases with
GAE, further correlation with clinical and magnetic resonance imaging findings will
be useful in preoperative planning for embolization.
