Step-by-Step Procedural Technique
Getting Started
Hepatic arterial mapping procedures with 99mTc-MAA administration are performed in the IR suite using intravenous moderate sedation. General anesthesia is rarely required and is limited to cases of patient preference or tolerance to narcotic medications commonly used for sedation and analgesia. To begin, routine arterial access is gained via the common femoral artery using sonographic guidance and a 21-gauge needle (Micropuncture Introducer Set; Cook Medical, Bloomington, IN). Vascular access is dilated to a 5F sheath (Pinnacle; Terumo, Somerset, NJ). While not used at the author's institution, the radial artery represents an alternative vascular access site.[6]
Diagnostic Arteriography
As previously noted, the aim of diagnostic arteriography performed during 90Y RE planning is to delineate hepatic vascular anatomy relevant to microsphere dosimetry and administration, and to identify extrahepatic vessels at risk for nontarget microsphere deposition. At the conclusion of the diagnostic component of the procedure, the IR operator should have a firm understanding of where tumor vascular supply is derived from, which vascular territories and vessels require treatment, the flow characteristics in these vascular beds, and the likelihood for nontarget microsphere deposition based on likely 90Y administration location. This is accomplished by systematic catheter interrogation of the celiac and hepatic vasculature.
To begin, celiac arteriography is performed using a 5F catheter such as SOS Omni Selective (AngioDynamics; Queensbury, NY), SIM 1 (Cook Medical), or C2 (Cook Medical) catheter. In the author's opinion, performance of an aortogram or superior mesenteric arteriogram is typically not necessary (in the absence of known variant vascular anatomy), as high-quality preprocedure cross-sectional imaging with CT or MR imaging routinely provides anatomic information about vascular anatomy—including aberrant vasculature—and portal venous patency. Furthermore, the iodinated contrast volume saved by deferring aortography and superior mesenteric arteriography can be applied to performing more hepatic arteriograms or undertaking more arteriography during embolization, if necessary. Nonetheless, celiac imaging carried through the venous phase may depict splenoportal patency via a delayed splenoportogram.
Hepatic arteriography is performed after placement of a coaxial 3F microcatheter such as a Renegade Hi-Flo (Boston Scientific, Natick, MA), or after exchange for a 4F catheter (Glidecath; Terumo). Use of a 4F catheter system can often improve arteriographic imaging and tumor visualization by providing higher iodinated contrast injection rate capability compared with most microcatheter systems, which may not be able to overcome very hyperdynamic hepatic arterial flow as is often seen in liver cirrhosis ([Fig. 1]). When performing hepatic arteriography, it is of paramount importance to achieve adequate filling of injected vascular beds to ensure complete filling of all arteries to guarantee visualization of both tumor and any potential nontarget vessels that may require embolization. Complete hepatic arteriography typically includes selective common hepatic, proper hepatic, left hepatic, and right hepatic arteriography, as well as segmental arteriography and/or super selective arteriography performed at the discretion of the IR physician. Some extrahepatic vessels—such as the right inferior phrenic artery—may on occasion require arteriographic interrogation, as these can contribute to parasitized blood flow to primary liver tumors. Typical iodinated contrast material injection rates used by the author for the celiac artery and hepatic or other branches relevant to 90Y RE planning are presented in [Table 1].
Table 1
Standard vessel injection rates
|
Artery
|
Iodinated contrast injection rate
|
Iodinated contrast injection volume (mL)
|
|
Celiac artery
|
−5 mL/s
|
16–20
|
|
CHA
|
3–4 mL/s
|
12–16
|
|
PHA
|
3–4 mL/s
|
12–16
|
|
Left hepatic artery
|
1–2 mL/s
|
8–10
|
|
Right hepatic artery
|
2–3 mL/s
|
10–15
|
|
Segmental HA
|
1–2 mL/s
|
6–8
|
|
GDA
|
2–3 mL/s
|
6–9
|
|
RGA
|
Manual injection
|
1–2
|
|
LGA
|
2–3 mL/s
|
8–12
|
|
Falciform artery
|
Manual injection
|
1–2
|
|
Phrenic artery
|
Manual injection
|
2–4
|
Abbreviations: CHA, common hepatic artery; GDA, gastroduodenal artery; HA, hepatic artery; LGA, left gastric artery; PHA, proper hepatic artery; RGA, right gastric artery.
Fig. 1 Hepatic arteriograms in same patient performed using microcatheter (a) and 4F catheter (b) demonstrate improved vessel filling with greater contrast injection capability of larger caliber catheter, with hypervascular tumor visualization (arrowheads).
Selection of 90Y Administration Site
Once a tumor vascular supply is identified, the IR operator should select an appropriate site for later 90Y microsphere administration. A suitable catheter position for 90Y RE should be in the lobar or segmental distribution of tumor beyond any potential nontarget vessels and at enough distance from branch points distal to the catheter tip to ensure homogeneous distribution of injected microspheres into arborizing vessels ([Fig. 2]). Presence of nontarget vessels distal to a planned 90Y RE should call for embolization of these branches or may require dose fractionation into separate branch vessels beyond the nontarget vessel origin, with microsphere delivery via different dose vials. In assessing tumor blood supply, the operator should also confirm that the entirety of all tumors or tumor parts for which treatment is planned are contained within a particular hepatic arterial injection representing the planned 90Y administration site. Angiographically, absent tumors or tumor portions may receive blood supply from other arterial sources, and lack of recognition of this finding can result in incomplete treatment ([Fig. 3]). From the tumor vascular supply, the IR operator can also assess factors that may impact selection of the particular 90Y microsphere product (resin vs. glass) to be used, if not already chosen; such parameters include vessel size and flow rate, as well as perfused liver bed size and vascularity. The operator may also use this opportunity to test the feasibility of any special maneuvers that may be used during 90Y microsphere administration, such as flow-directed catheter repositioning.[7] Finally, the IR physician should scrutinize angiographic images for findings that may suggest the presence of a high lung shunt fraction, such as arterioportal shunting ([Fig. 4]) or hepatic artery to hepatic vein shunting/fistulae. Such findings may call for measures to reduce shunting, such as large particle embolization or transarterial chemoembolization as a bridge to 90Y RE ([Fig. 5]).[8] Excessive shunting that cannot be reduced using such techniques, and that results in persistently high lung shunt fraction (LSF), may preclude safe 90Y RE.
Fig. 2 Selection of catheter position for 90Y RE. Coronal reformatted contrast-enhanced CT scan (a) shows two hepatocellular carcinoma nodules (arrowheads) within right hepatic lobe. Arteriogram (b) displays suitable microcatheter position for lobar 90Y RE, with tip (arrow) in right hepatic artery in vascular distribution of both tumors (arrowheads), but sufficiently proximal to branching to allow homogeneous microsphere dispersal.
Fig. 3 Incomplete treatment due to extrahepatic tumor blood supply. Axial contrast-enhanced CT scan (a) demonstrates segment 7 hepatocellular carcinoma (arrowheads). Arteriogram (b) shows hypervascular tumor (arrows). However, note absent perfusion along posteromedial margin (arrowheads), which was unnoticed prior to 90Y RE. Posttreatment axial contrast-enhanced CT scan (c) displays partial tumor response, with persistent viable tumor enhancement (asterisk). Arteriogram performed during retreatment (d) reveals tumor blood supply (arrowheads) via inferior phrenic artery, which was treated with transarterial chemoembolization.
Fig. 4 Arterioportal shunting. Axial contrast-enhanced CT scan (a) shows large primary liver tumor (arrowheads). Arteriogram (b) performed during 90Y RE planning demonstrates extensive arterioportal shunting, with early portal vein visualization (black arrowheads) during late arterial phase of imaging (black arrows delineate common hepatic artery). Shunt subsequently closed with large particles.
Fig. 5 Chemoembolic shunt reduction to allow 90Y RE. Axial contrast-enhanced CT scan (a) demonstrates left hepatic lobe infiltrative tumor with portal vein invasion. 99mTc-MAA scan (b) shows high lung shunt fraction measuring 30%. Axial contrast-enhanced CT scan (c) performed after transarterial chemoembolization shows high attenuation chemoembolic material (arrowheads) in left hepatic lobe tumor. Repeat 99mTc-MAA scan (d) obtained following chemoembolization reveals lung shunt fraction reduced to 22%. 90Y RE to left liver lobe subsequently performed at later date.
Nontarget Vessel Embolization
The multitude of vessels at risk for potential nontarget microsphere deposition have been well described in the literature, and include the GDA, RGA, falciform artery ([Fig. 6]), and cystic artery, among others.[4] The decision of whether to embolize a potential nontarget vessel can often be challenging. Early in an IR operator's 90Y RE practice, it is probably prudent to occlude all potential nontarget vessels that can safely be embolized—most frequently the GDA and RGA—using metallic coils such as MicroNester coils (Cook Medical), to avoid radiation-induced ulcers and to ensure a high level of procedural safety during initial experience with this therapy. As one's know-how expands and clinical practice matures, embolization of such extrahepatic vessels may not be considered mandatory if 90Y RE can be performed at a safe distance from the vessel origin, per the judgment of the IR physician.[9] However, since arterial stasis is a risk factor for gastrointestinal ulceration,[10] embolization should be strongly considered when a high 90Y microsphere load is to be used for therapy, as in the case of resin microspheres, or when small or low flow vascular territories are to be treated. In the author's practice, nontarget vessel embolization is typically performed when resin microspheres are to be used for treatment, when the prospective 90Y administration site is close in proximity to the GDA or RGA, for all arterial variants arising from an intrahepatic artery (e.g., accessory gastric artery arising from left hepatic artery, [Fig. 7]), and prior to left lobe 90Y therapies (given the proximity of the 90Y administration site to the GDA and RGA). While embolic protection of the cystic artery in the case of right lobar 90Y RE is feasible,[11] this is not typically pursued by the author, given the low overall risk for biliary complications after right hepatic lobe 90Y RE[12]; instead, 90Y RE administration that is planned for proximal to the cystic artery is treated with a weeklong course of antibiotic coverage.
Fig. 6 Arteriogram performed for 90Y RE planning illustrates typical falciform artery (arrowheads) arising from segment 4 branch of left hepatic artery.
Fig. 7 Accessory gastric artery. Left hepatic arteriogram (a) shows branch vessel (arrowheads) supplying hypervascular “tuft” (arrows) in abdominal left upper quadrant. Arterial (b) and venous (c) phase angiograms performed after microcatheter interrogation reveal gastric fundal enhancement (arrowheads) with venous drainage via left gastric vein (arrowheads), confirming vessel to be accessory gastric artery.
Embolization Technique
From a technical standpoint, embolization of a medium-sized vessel such as the GDA is generally straightforward. Most challenges in GDA embolization arise with placement of the last coil near the vessel origin from the common hepatic artery, where careless technique can result in coil migration. Tips to successful deployment of the last coil include use of the “anchor” technique ([Fig. 8]) and use of a supporting 4F catheter advanced to the GDA origin to ensure avoidance of microcatheter recoil and dislodgment from the vessel during coil deployment ([Fig. 8]). Detachable coils or vascular plug devices may also be useful in this circumstance, given the capacity for precise placement ([Fig. 9]) and for potential removal if malpositioned.
Fig. 8 Anchor technique shown on postembolization arteriogram after gastroduodenal artery (GDA) embolization. Note proximal coil (black arrowheads) anchored into GDA side branch (arrow) to ensure coil positional stability, as well as base catheter tip (white arrowhead) advanced to near GDA origin for extra support.
Fig. 9 Plug embolization. Postembolization common hepatic arteriogram shows plug device (arrowheads) accurately positioned at the origin of gastroduodenal artery.
RGA embolization is often a source of frustration. An obvious key to successful embolization of this vessel is catheterization. To this end, the author always performs a common hepatic arteriogram at full magnification to clearly identify the RGA origin ([Fig. 10]), which assists with successful wire cannulation. Once catheterized, the author typically embolizes this vessel using 3-mm coils “unsheathed” from the microcatheter using a wire pusher, to avoid pushing the microcatheter out of the vessel during aggressive coil advancement. If the RGA cannot be catheterized primarily, retrograde catheterization and embolization via a left gastric artery to RGA arcade—if present—is a useful and well-described approach ([Fig. 11]). If embolization of the RGA or another vessel is technically unsuccessful during the planning arteriogram procedure, the IR operator should remember that he/she will have a second opportunity to attempt the embolization at the time of 90Y administration. Another option is to use an antireflux catheter for 90Y microsphere administration. Finally, the decision to push versus inject coils is usually at the discretion of the primary IR operator. The author's preference is to inject most coils and to reserve coil pushing to cases of small vessel (e.g., RGA) embolization and for last coil deployment near a vessel origin from a parent artery.
Fig. 10 Magnified common hepatic arteriogram nicely delineates right gastric artery origin (arrowheads) from right lateral wall of proper hepatic artery.
Fig. 11 Retrograde right gastric artery (RGA) embolization for patient depicted in [Fig. 10]. Left gastric arteriogram (a) portrays complete arcade (arrowheads) with RGA along lesser curvature of stomach. Fluoroscopic images (b) and (c) display sequential microcatheterization across arcade, with successful coil embolization (arrowheads) illustrated in fluoroscopic image (d).
While everyone performing mapping arteriography prior to 90Y RE procedures will inevitably encounter a coil migration incident, the response to this mishap is important. While it is desirable to remove a migrated coil from a hepatic circulation for which treatment is desired, too much or careless manipulation can also result in injury such as vessel dissection. In the circumstance of coil migration into the hepatic circulation or even herniation of a coil into a parent vessel, the author will attempt to remove or retrieve the coil if a free end is available for capture ([Fig. 12]), aiming to avoid overmanipulation that may lead to vessel injury. However, if snaring the coil is not technically feasible, 90Y RE is often not precluded, with treatment possible through a coil pack and/or collateral tumor supply ([Fig. 13]). An innovative approach to dealing with coil migration into the vascular distribution of prospective 90Y RE is intrahepatic vascular flow redistribution, a strategy used to consolidate arterial flow to tumors by embolizing accessory feeders to allow single vessel 90Y RE.[13]
[14] In this scenario, complete occlusion of the branch vessel into which coil migration occurred may be used to develop collateral blood supply from other intrahepatic arteries to allow 90Y administration ([Fig. 14]); while not an ideal circumstance, this approach may be the most successful in some patients.
Fig. 12 Coil malposition. Common hepatic arteriogram (a) demonstrates herniation of gastroduodenal artery (GDA) coil (arrows) into parent artery, which could limit later 90Y RE; second coil (white arrowhead) located in right gastric artery. GDA coil retrieved by snaring free end (black arrowhead), and GDA then embolized again with better result, shown in arteriogram (b).
Fig. 13 Coil migration. Celiac arteriogram (a) shows right hepatic lobe hypervascular liver tumor (arrowheads). Arteriogram (b) performed after inadvertent right hepatic artery coil migration (arrowhead) during gastroduodenal artery embolization displays poor tumor perfusion. Coil could not be retrieved. Nonetheless, arteriogram (c) performed during 90Y RE ∼2 weeks later demonstrates tumor perfusion through coil pack and via collateral vessels; 90Y RE successfully performed.
Fig. 14 Coil migration resolved with intrahepatic vascular flow redistribution (case courtesy of Brandon K. Martinez, MD, Corvasc MDs PC, Indianapolis, IN). Axial contrast-enhanced CT scan (a) shows right hepatic dome hepatocellular carcinoma (arrowhead), for which 90Y RE therapy planned. Arteriogram (b) reveals unintentional coil migration (arrowhead) into right hepatic artery from attempted gastroduodenal artery embolization. As coil could not be retrieved, right hepatic artery intentionally further coil embolized (arrowheads in image c) to induce left-to-right intrahepatic arterial collateralization (arrowheads in image d). Right hepatic lobe 90Y RE then successfully performed via left hepatic artery segment 4 branch, as depicted on Bremsstrahlung scan (e).
Special Considerations
As has been noted by others, 90Y RE treatment of the left hepatic artery may be precarious, as this vessel more commonly harbors relevant anatomic variants compared with the right hepatic artery. Examples include a gastrohepatic trunk ([Fig. 15]), as well as accessory gastric, esophageal, and phrenic ([Fig. 16]) arteries that may go unrecognized and which may increase the risk for nontarget 90Y delivery. Moreover, compared with the right hepatic artery, the left hepatic artery is typically smaller in caliber, has a shorter undivided segment that does not permit as distal microcatheter positioning, supplies a smaller liver volume, and possesses a less capacious vascular bed, all of which theoretically raise the risk for embolic stasis, reflux, and/or vascular saturation. With these considerations in mind, the author routinely pursues GDA and RGA embolization in the setting of unilateral left hepatic lobe 90Y RE, knowing that the incidence of gastrointestinal ulceration is likely low when protective measures are applied. In cases of bilobar malignant disease, however, the author has occasionally adopted a treatment approach that omits left hepatic lobe 90Y (and risk for gastrointestinal ulceration) altogether and employs a locoregional strategy that potentially affords some practical, methodological, and logistical benefits. In cases of bilobar tumor, the author performs left hepatic lobe transarterial chemoembolization—without GDA or RGA embolization—at the time of mapping arteriography for 90Y planning, and subsequently pursues 90Y RE to the right hepatic lobe the usual 10 to 14 days later. Although nontarget chemotherapy may result in gastrointestinal side effects as well,[15] the risk is anecdotally less than that with radiotherapy, and the utilization of a radiographically visible chemoembolic therapeutic agent that may be administered in small aliquots under direct fluoroscopic visualization helps avoid reflux and nontarget deposition through real-time monitoring in contrast, 90Y microspheres cannot typically be infused in such a controlled and directly monitored manner at present (although some operators inject 90Y resin particles as a suspension in iodinated contrast material). Furthermore, such treatment consolidation allows earlier completion of treatment cycle, as patients typically achieve whole liver therapy in 10 to 14 days over two procedures, as opposed to 5 to 6 weeks over three procedures for routine bilobar 90Y therapy (in which planning arteriography is performed at time zero followed by treatment of one liver lobe 10–14 days later and the second liver lobe 1 month after that).[5] Another potential theoretical benefit of this approach that may be exploited in research studies is the capability for within-patient comparison of locoregional treatment efficacy (chemoembolization vs. 90Y RE), although such a comparison could be confounded by factors such as therapy lead time bias as well as differences in baseline tumor characteristics, such as size. While the author does not have a substantial enough patient cohort on which to report at this time, this approach has anecdotally been found by the author to provide an efficient means to treat bilobar liver tumor patients. As a final note, intrahepatic flow redistribution could also be used in the scenario described, with coil embolization of the left hepatic artery and whole liver treatment via the right hepatic artery.
Fig. 15 Gastrohepatic trunk. Axial contrast-enhanced CT scan (a) shows typical location of anomalous left gastric artery (black arrowhead) within fissure for ligamentum venosum; left hepatic lobe exophytic hepatocellular carcinoma also present (white arrowhead). Left gastrohepatic trunk arteriogram (b) depicts numerous gastric branches (arrowheads) at risk for nontarget 90Y microsphere deposition during hypervascular tumor (arrows) therapy.
Fig. 16 Left hepatic arteriogram reveals anomalous origin of left interior phrenic artery (arrowheads) from left hepatic artery. Embolization of this vessel would be required prior to left hepatic lobe 90Y therapy.
99mTc-MAA Injection and Imaging, and LSF Calculation
As a final step of the planning arteriogram procedure, 4 to 5 mCi of 99mTc-MAA is administered to the whole liver for 99mTc-MAA scanning. 99mTc-MAA should be prepared and called to the IR procedure suite as close to the time of administration as possible, to avoid 99mTc-MAA degradation and pulmonary transit that may lead to spurious LSF elevation.[5] To this end, at the author's institution, 99mTc-MAA is typically requested from the nuclear medicine department approximately 5 minutes prior to injection. 99mTc-MAA may be injected from the common or proper hepatic arteries (depending on whether the gastroduodenal and/or RGAs are embolized) in cases of standard liver vascular anatomy. In cases of aberrant arterial anatomy, the 99mTc-MAA is fractionated into all liver feeding branches, which requires catheter and/or microcatheter repositioning between administrations. After 99mTc-MAA injection, all devices are removed, and hemostasis is achieved with manual compression or a vascular closure device.
For 99mTc-MAA scanning at the author's institution, planar chest and abdomen images are performed within 30 minutes of 99mTc-MAA intra-arterial injection. Patients are positioned supine under a dual-detector gamma camera (SkyLight; Philips, the Netherlands). Both anterior and posterior projections are obtained until 1 million counts are collected for the abdomen, and scan time is recorded. The same scan time is applied to chest and total counts in the chest field-of-view are recorded. To calculate the percentage of hepatopulmonary shunting, regions-of-interest (ROIs) are drawn around the liver and both lungs. Geometric means for liver and lungs are obtained. Hepatopulmonary shunt ratio is calculated using the following formula:
% LSF = (total lung counts/total lung + total liver counts) × 100
Abdominal shunt fraction, defined as total extrahepatic abdominal counts/total extrahepatic abdominal + total liver counts × 100, is similarly calculated using ROIs drawn around the liver and extrahepatic abdomen.
In cases in which repeat 90Y RE treatment is planned in a relatively remote time frame (more than 6 months) after initial planning arteriography and 99mTc-MAA scanning, repeat mapping arteriography and 99mTc-MAA LSF calculation should be performed to identify any changes in hepatopulmonary shunt fraction that may impact 90Y RE dosimetry. As a final note, while a distinct planning arteriography session with 99mTc-MAA scanning is currently considered mandatory for 90Y RE therapy, this approach may shift in the future, given recent reports of consolidated treatment protocol consisting of same day 99mTc-MAA scanning and 90Y RE therapy,[16] and future studies aiming to assess the safety of 90Y RE treatment protocol excluding 99mTc-MAA scanning in tumors known to have low LSFs.[17]
