Feline chylothorax is a potentially debilitating disease with multiple etiologies including cardiac disease,1 mediastinal masses,2–3 thromboembolic disease,4 and heartworm disease.5 When these disorders are discovered, treatment is aimed at the underlying disease process. Unfortunately, the most common etiology of feline chylothorax is idiopathic,6 and when medical management fails, surgery is often indicated.7 Given the vast variability in thoracic duct anatomy in the dog and cat, imaging of the thoracic duct and its tributaries prior to thoracic duct ligation can be an essential aid to surgical planning. A myriad of different percutaneous lymphangiography techniques has been published using diagnostic imaging to identify the thoracic duct.8–12 It has been the authors’ experience that these techniques may not be viable options in all cases and may not work effectively in every patient especially if the lymph nodes to be injected are small or poorly accessible. Additionally, techniques such as mesenteric lymph node injection require extensive ultrasound guidance skills and may or may not be possible depending on the location and size of the mesenteric lymph nodes. Other published imaging techniques such as the injection of contrast material into the popliteal lymph node or metatarsal region followed by computed tomography (CT) have been shown to be effective in opacifying the thoracic duct.10–11 However, given efferent drainage patterns identified in similar species, these techniques bypass the intestinal and hepatic lymphatic vessels that are the major tributary to the intestinal trunk, and in clinical cases of chylothorax or cases of both chylothorax and chylous abdominal effusion, important lymphatic anomalies or duct ruptures arising from the intestinal and hepatic lymphatics or the intestinal trunk theoretically could be missed with these imaging techniques.13
Anatomically, in cats, 70% of the thoracic duct lymph originates from the intestines and 30% is produced by the liver.13 Mesenteric lymph node injection of nonionic iodinated contrast material has proven useful in delineating the intestinal lymphatic, cisterna chyli, thoracic duct, and its tributaries using CT.8–9 We hypothesized that indirect lymphography via hepatic parenchymal injections of nonionic iodinated contrast material would lead to opacification and positive delineation of the hepatic lymphatics, cisterna chyli, thoracic duct, and its tributaries using CT. The specific aims of this prospective pilot study were to (1) determine if percutaneous parenchymal injections of nonionic iodinated contrast material (iopamidol) would lead to cisterna chyli and thoracic duct opacification on CT; and (2) determine the time to peak opacification of the thoracic duct using this technique.
Materials and Methods
Animals
Six purpose-bred domestic short-haired cats were acquired from a commercial vendor with a mean age of 5.5 months (range, 5 to 6 months) and a mean weight of 6.15 kg (range, 5.9 to 6.9 kg). The inclusion criterion for enrollment into the study was a normal physical exam, complete blood count (CBC), and biochemistry panel. All procedures were approved by the institutional animal care and use committee. After completion of the project, all cats were adopted. All cats were housed in an institutionally approved cattery and fed an institutionally approved diet.
Anesthesia
All cats were placed under anesthesia twice at 3-month intervals for completion of the study. Cats were placed and maintained under general anesthesia by the institutional anesthesiology service under the direction of board-certified specialists in veterinary anesthesia and analgesia on each of 2 occasions 3 months apart. Following a 12-hour fast, the cats were placed into an induction chamber and administered isoflurane in oxygen until recumbent. Cats were then masked with isoflurane in oxygen until they could be intubated. A cuffed endotracheal tube was then placed and cats received isoflurane in oxygen (FIO2 = 60%), to effect, for maintenance of anesthesia. A 22-gauge IV catheter was placed in a cephalic vein and atropine sulfate (0.02 mg/kg, IM; West-Ward Eatonton) and buprenorphine hydrochloride (0.02 mg/kg, IV; Reckitt Benckiser Pharmaceuticals) were administered. All cats were administered lactated Ringer solution at a rate of 5 ml/kg/h. Cats were mechanically ventilated using a pressure-controlled ventilator at a rate of 10 breaths/min. Doppler blood pressure monitoring was used to ensure adequate blood pressure throughout the procedure.
CT lymphangiography
At each of the 2 time points, cats were placed in dorsal recumbency and the fur overlying the hepatic parenchyma and cranial abdomen was clipped away and aseptically prepared for percutaneous hepatic injection. 2 ml of iopamidol (Isovue 370) was injected via ultrasound guidance into either a right or left-sided liver lobe using a 27-gauge 1.25-inch needle attached to a preloaded 3-cc syringe and high-pressure T-port. The right or left liver injection site was predetermined randomly using online randomization software (randomizer.org). Each cat received left- and right-sided hepatic parenchymal injections in an effort to use each cat as its own control. A right-sided injection was defined as an injection into a liver lobe to the right of the gallbladder and a left-sided injection was defined as an injection to the left of the gallbladder and to the left of the midline. The injection was monitored real time under ultrasound guidance, and care was taken to ensure that hepatic parenchymal injection was performed and extravasation or injection into the gall bladder or large vessels was avoided. When necessary, the needle was repositioned. CT images of the cranial abdomen and thorax were taken at 5-, 10-, and 15-minute time points and were acquired at 120 kV and 150 mA and 0.6-mm slice thickness (GE Lightspeed multislice helical scanner) (Figures 1–3). Images were acquired in standard and thorax algorithms and were viewed initially with a window width of 350 Hounsfield Units (HU) and a window level of 50 HU. Manipulation of this initial window width and level was allowed to facilitate a better definition of structures. All data analysis was performed on a dedicated Picture Archiving and Communication System (PACS) workstation using e-Film Workstation (IBM Watson Health). Time to peak opacification of the thoracic duct was subjectively determined by comparing the relative opacity in the thoracic duct at the level of the T12 vertebral body between time points. Additionally, overall visualization and opacification of the thoracic duct and its tributaries were subjectively graded by a board-certified radiologist (EGJ) as excellent, good, fair, or absent. Excellent was defined as marked opacification of the cisterna chyli and thoracic duct with discrete visualization of the thoracic duct branches. Good was defined as moderate opacification of the thoracic duct and cisterna chyli with discrete visualization of the thoracic duct branches. Fair was defined as mild opacification of the thoracic duct and cisterna chyli with enough contrast present to define these as discrete structures and count the number of thoracic duct branches. In cases of absent opacification at the 15-minute time point, an additional 2 ml of contrast material was injected into the same prescribed side of the liver after which the same CT protocol as previously described was followed for a second time. Care was taken to avoid the initial injection site and to be remote as possible to the initial injection site while maintaining safety and ensuring a parenchymal injection. After 3 months and under a second anesthesia episode, the CTL procedure was repeated this time injecting the contralateral side of the liver from that previously injected.
A—Transverse CT image at the level of T12 showing excellent opacification of the thoracic duct 5 minutes postpercutaneous injection of contrast material into the hepatic parenchyma (arrow). B—Transverse CT image at the level of T1 showing fair opacification of the thoracic duct 5 minutes postpercutaneous injection of contrast material into the hepatic parenchyma (arrow).
Citation: American Journal of Veterinary Research 84, 2; 10.2460/ajvr.22.08.0147
Transverse CT image of the hepatic lymph nodes showing opacification of 1 of the hepatic lymph nodes (*). Contrast can be seen in the hepatic parenchyma postinjection (arrowhead). A lymphatic tributary can be seen adjacent to the hepatic lymph node (arrow).
Citation: American Journal of Veterinary Research 84, 2; 10.2460/ajvr.22.08.0147
This is a 3-dimensional rendering of the thorax and cranial abdomen 5 minutes posthepatic injection with contrast material. The injection site can be seen (*). The intestinal trunk and associated lymphatic tributaries are opacified leading to the cisternal chyli (arrowheads). The thoracic duct is opacified throughout its entire length (arrow).
Citation: American Journal of Veterinary Research 84, 2; 10.2460/ajvr.22.08.0147
Postprocedure evaluation of hepatic function
Initial baseline CBCs, physical exams, and serum biochemistry panels were obtained. These were compared to CBCs and physical exams, and serum biochemistry panels obtained 3 months after the initial hepatic contrast injections immediately prior to the second anesthetic procedure and hepatic contrast injections in 5 out of 6 cats. In 1 cat, bloodwork was inadvertently not drawn prior to the second anesthetic episode. Initial ultrasound examination of the liver was obtained at baseline prior to the first intrahepatic injection and compared to hepatic ultrasounds performed 3 months later immediately prior to the second round of intrahepatic contrast injections. No further bloodwork or ultrasound examinations of the liver were performed after the second anesthetic episode and hepatic injections in any cats.
Results
CT lymphangiography
The results of CT lymphangiography (CTL) after intrahepatic parenchymal injection into the left and right liver in 6 cats are summarized (Table 1). Eleven intrahepatic injection data points from 6 cats over 2 anesthetic episodes were available for review. One CTL data file was corrupted and was not able to be used. Seven out of 11 hepatic contrast injections yielded a diagnostic study. Five out of 11 were graded as excellent, 0/11 were graded as good, 2/11 were graded as fair. Time to peak opacification of the thoracic duct postintrahepatic injection was determined to be 5 minutes in all cats graded as excellent opacification, and opacification was equal at 5 minutes and 10 minutes for the 2 studies graded as fair opacification. All 15-minute intrahepatic injections were nondiagnostic with a complete absence of contrast material in the thoracic duct and cisternal chyle. Right-sided hepatic injections yielded a diagnostic study in 4/5 attempts (1 data set was corrupted), and left-sided hepatic injections yielded a diagnostic study in 3/6 attempts. In the 4 studies with absent opacification, redosing contrast material was unsuccessful in producing cisterna chyli or thoracic duct opacification. A small volume of peritoneal leakage of contrast material was detected in all cats surrounding and localized to the perihepatic parenchyma. This localized contrast leakage did not interfere with the interpretation of the anatomy of the cisterna chyli. All cats had a visible parenchymal bolus of contrast material identified with ultrasound and CT posthepatic injection. All boluses were confirmed to be deep within the hepatic parenchyma on CT. Two cats required minor needle repositioning to avoid vessels and ensure hepatic parenchymal injection. All cats with diagnostic lymphangiograms had evidence of transit of contrast through the hepatic lymph nodes, mesenteric lymphatics, and cisterna chyli and had concurrent opacification of the thoracic duct. There was no apparent difference in the appearance of the parenchymal contrast bolus or degree of peritoneal contrast leakage on CT or ultrasound between diagnostic and nondiagnostic studies. The mean total anesthetic time was 52 minutes (range, 45 to 60 minutes). The mean total CT time was 29 minutes (range, 25 to 35 minutes).
Results of CT lymphangiography (CTL) after intrahepatic parenchymal injection into the left and right liver in 6 cats.
| Cat number/left- or right-sided injection | Subjective quality |
|---|---|
| 1 | |
| Right | Excellent |
| Left | Nondiagnostic |
| 2 | |
| Right | Excellent |
| Left | Nondiagnostic |
| 3 | |
| Right | Missing data |
| Left | Fair |
| 4 | |
| Right | Excellent |
| Left | Excellent |
| 5 | |
| Right | Nondiagnostic |
| Left | Nondiagnostic |
| 6 | |
| Right | Fair |
| Left | Excellent |
Postprocedure evaluation of hepatic function
No ultrasonographic abnormalities to the hepatic parenchyma were detected pre- or postprocedure or at any time during the study with the exception of visualization of the injection site at the time of parenchymal injection. The results of serum biochemical profiles for 5 out of 6 cats are summarized (Table 2). Serum biochemical parameters were within the normal range at baseline prior to the first CTL study being performed. At 3 months after the first procedure and immediately before the second anesthetic episode was performed, 2 out of 5 cats showed a moderate increase in serum alanine aminotransferase (132 and 484 IU/L; reference range, 27 to 101 IU/L), and 1 cat had a mild increase in aspartate transaminase (81 IU/L, reference range, 17 to 58 IU/L). The remaining cats had normal serum biochemistry panels postprocedure.
Summary of serum biochemical profiles of 5 cats pre- and postcomputed tomography lymphangiography (CTL) after intrahepatic parenchymal injection of iodinated contrast material (iopamidol).
| Reference range | Pre-CTL (median, range) | Post-CTL (median, range) | |
|---|---|---|---|
| Albumen (g/dL) | 2.2–4.6 | 3.9 (3.2–4.1) | 3.7 (3.5–4.1) |
| Globulin (g/dL) | 2.8–5.4 | 2.6 (2.2–2.9) | 2.6 (2.2–3.0) |
| Alanine aminotransferase (IU/L) | 27–101 | 54 (45–64) | 80 (57–484) |
| Aspartate aminotransferase (IU/L) | 17–58 | 26 (19–44) | 27 (23–81) |
| Alkaline phosphatase (IU/L) | 14–71 | 29 (1–53) | 46 (39–56) |
| Cholesterol (mg/dL) | 89–258 | 74 (70–114) | 97 (90–175) |
Discussion
Intrahepatic parenchymal injection of nonionic iodinated contrast material was successful in opacifying and creating diagnostic CTL studies of the cisterna chyli and thoracic ducts in 64% of percutaneous intrahepatic injections. Other thoracic duct imaging techniques in cats report higher success rates of up to 100%.9–10 These techniques include mesenteric and popliteal lymph node injections of nonionic iodinated contrast material. Therefore, this technique may not be the first choice for imaging the thoracic duct but may be useful to employ if other techniques fail to yield diagnostic results. One potential benefit to this technique is the opacification of the hepatic and intestinal lymphatics, which may be bypassed by other techniques given the normal anatomic efferent lymphatic flow patterns.14 To the authors’ knowledge, this is the first time the hepatic lymphatic contribution to the thoracic duct has been imaged using CTL.
It is unknown at this time why some cats had what was graded as excellent thoracic duct lymphangiography results and some had absent contrast enhancement or nondiagnostic results. There appeared to be no difference in the ultrasound or CT imaging characteristic between injections or injection sites. All injections appeared to diffuse through the hepatic parenchyma, but perhaps there were subtle subgross anatomic differences to the sites of contrast injection that were not evident on ultrasound or CT, which led to the discrepancy in hepatic lymphatic uptake of contrast material. Contrast dosages were higher in some cats (4 ml with redosing of contrast), but despite the increased contrast dose, opacification of the thoracic duct system was unsuccessful. The total delivered dose of 4 ml total (after the second dosing) is higher than other studies9–10 that used 1.5 or 2 ml for injections although these studies were using direct lymph node injections (lymphadenography) as opposed to indirect lymphangiography. Alternatively, lymphatic variability between individuals or individual liver lobe injections sites may have led to the lack of success of this technique
Of the right-sided hepatic injections, 80% resulted in diagnostic opacification of the thoracic duct and cisterna chyle while only 50% of left-sided injections yielded the same result. This fact must be interpreted with caution due to the low sample size with right-sided injections only having 1 more successful result than left-sided injections. Additionally, having a nondiagnostic study with a left-sided hepatic injection did not necessarily correlate with a nondiagnostic study with a right-sided hepatic injection. In fact, some cats having a study graded as nondiagnostic or fair with hepatic injection on one side had a study graded as excellent on the contralateral side. One cat had nondiagnostic studies after intrahepatic injections on both left and right sides. Time to peak opacification for all diagnostic studies was between 5 and 10 minutes with all studies graded as excellent, having a 5-minute peak opacification. This likely is a sequela of the rate of uptake of the contrast material and rate of passage of the contrast material through the lymphatic system. All contrast material was cleared from the thoracic duct within 15 minutes or was never present. This is likely due to the rate of transport of contrast material through the lymphatic system or in the case of the nondiagnostic studies that contrast material was never delivered to the thoracic duct or its tributaries. Studies that required repeat injections had time points in excess of 30 minutes (postinitial injection), which still did not show opacification of the thoracic duct. It is possible that some cats had more rapid uptake and clearance of the contrast material through the thoracic duct and its tributaries, which may have been missed by the initial 5-minute timeframe; however, the contrast was present at both the 5- and 10-minute time points in cats with diagnostic studies.
All of the cats demonstrated a small volume of localized perihepatic peritoneal leakage of contrast material. This material did not interfere with the anatomic evaluation of the cisterna chyli; however, it is possible that a large volume of contrast could be spilled into the peritoneal cavity obscuring important lymphatic structures.
Two of the cats had postprocedural elevations in liver enzymes 3 months postinjection of contrast material. It is unknown if these elevations were due to the injection of contrast material or other underlying diseases since liver biopsies were not performed. Unfortunately, funds were not available to run a third biochemistry panel to determine if liver enzymes had returned to normal in these patients. It should be noted that all cats showed no postprocedural hepatic sonographic changes, were clinically normal for the duration of the study, and were successfully adopted without noted or reported complications. All hepatic injection sites were not visible at the 3-month postinjection time interval, and all liver ultrasounds were normal at this time. A literature search did not identify any articles discussing intrahepatic injections of iopamidol and its effects on liver enzymes, and this likely is the first description of this technique. It is anticipated that there would be elevated hepatic enzymes in the immediate postprocedural phase, and this should be considered in evaluating liver enzymes in clinical patients.
There were several limitations to this study, one being a small sample size. This small sample size makes it difficult to draw statistical conclusions. Moreover, these were normal cats and it is unknown at this time if indirect hepatic lymphangiography will produce a diagnostic study in clinical cases of feline chylothorax or if time to peak opacification of the thoracic duct will change. An additional limitation was not having liver biopsies in the subset of cats with elevated liver enzymes to identify causality.
While percutaneous hepatic parenchymal injection of nonionic iodinated contrast material has not proven to be as successful as other techniques, it still may have utility for surgical planning or diagnosis in cases of chylothorax when other CTL methods fail to opacify the thoracic duct and its tributaries. This technique, when successful, does allow for visualization of the hepatic contribution of the mesenteric lymphatics, cisterna chyle, and thoracic duct with peak opacification at approximately 5 to 10 minutes postinjection.
Acknowledgments
This study was funded in part with a grant from the University of California-Davis Center for Companion Animal Health.
The authors declare there were no conflicts of interest.
This study utilized the Animal Research: Reporting of In Vivo Experiments (ARRIVE) guidelines where applicable.
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