Tc-99m sulfur colloid SPECT-CT and assessment of functional liver reserve after Y90 radioembolization: A case report

Highlights • Y90 radioembolization has shown feasibility for downstaging patients for resection.• Functional liver reserve is a choice pre-surgery/postradioembolization measurement.• Tc-99 m Sulfur Colloid SPECT-CT can assess functional liver reserve before surgery.


Introduction
Yttrium-90 (Y90) radioembolization is an effective treatment for unresectable hepatocellular carcinoma (HCC) that has shown feasibility as a tool for downstaging patients for resection [4][5][6][7][8]. However, postradioembolization, and prior to segmentectomy or lobectomy, it is important to assess the percentage of functioning liver reserve to better understand a patient's prognosis and potential approaches to management. Tc-99 m sulfur colloid (Tc-99 m SC) is a diagnostic tracer that is taken up by reticuloendothelial cells of the liver and, when used in conjunction with single-photon emission computed tomography (SPECT-CT) and planar imaging, correlates with liver function in patients with HCC [1,2]. We specifically utilized this agent to assess normal functional liver reserve post-Y90 radioembolization and prior to surgery in a case where neither the patient nor the surgeon would have considered surgery as a feasible treatment option. The work has been reported in line with the SCARE criteria [9].

Case presentation
A 64-year-old man, referred by a private doctor, walked into the accident and emergency department of our major regional hospital. He had been experiencing abdominal discomfort for over a month, weight loss and poor appetite. He was a chronic smoker and user of alcohol, with benign colon polyps. He reported having no fever, tea-colored urine, or symptoms of gastrointestinal bleeding. Hard, irregular hepatomegaly was present on physical exam, and liver ultrasound revealed cirrhosis and bilateral liver masses. On admission, his liver function was within normal range. However, alpha feto protein (AFP) was 4522 ng/mL (Table 1)  the liver, without evidence of portal vein thrombus or extrahepatic spread. The patient was classified as having Barcelona Clinic Liver Cancer (BCLC) stage B disease, and a Child-Pugh score of A (Fig. 1). Hepatic angiogram revealed that approximately 90% of the tumor vasculature was supplied by right hepatic artery branches. Both portal veins were compressed by the tumor, but still patent. Downstaging the tumor was a priority. Y90 radioembolization has been shown to contribute to a reduction in tumor size in patients with bulky disease, and was considered as a therapeutic choice. At 5 weeks post admission, Tc-99 m macroaggregated albumin (Tc-99 m MAA) SPECT-CT was utilized to assess the lung shunting percentage and tumor-to-normal (T/N) ratio [10], which were 9.06% and 1.56, respectively, and to determine the patient's eligibility for Y90 radioembolization. In an attempt to promote a better T/N ratio, coil embolization of 2 branches of the right hepatic artery supplying S7 and S8, which did not supply the tumor, was conducted. Tc-99 m MAA SPECT-CT was repeated one week later at which time the T/N ratio improved to 3.1. Y90 radioembolization proceeded with administration of 3.7 GBq SIR-Spheres resin microspheres (SIRTEX Medical; Sydney, Australia): 0.92 GBq and 2.78 GBq to the left and right hepatic artery, respectively [11].
On follow-up CT scan of the liver 3 months after Y90 therapy, the tumor was reduced to 6.5 cm (Fig. 2). However, while the patient's bilirubin levels remained within normal range, AFP levels began to rise, suggesting residual tumor activity ( Table 1). At that time, resection was considered.
According to the follow-up CT scan, the volume of the lateral segment (S2 + S3) and the total liver volume were analyzed by Syngo.Via (Siemens Healthineers; Erlangen, Germany) at 621 mL and 1324 mL, respectively (Fig. 3a,b). The functional remnant volume (FRV) for right hepatectomy was 47% by volume (FRV% = volume of reserve lobe / whole liver volume X 100%).
An indocyanine green (ICG) dye test, used to estimate hepatic functional reserve and ICG retention at 15 min, was 22%, higher than the common parameter for right hepatectomy, <14%. [12,13] After discussion with surgeons, oncologists, and radiologists, at five and a half months post Y90 radioembolization, a Tc-99 m SC SPECT-CT scan was introduced. An outside facility prepared 3 mCi of Tc-99 m SC, heated without filtrating [1], with the anticipation that these larger particles would accumulate mainly in the liver and spleen. The colloid was injected intravenously. Twenty minutes after injection, planar images (abdomen) and SPECT-CT with attenuation correction were performed. A dual-head SPECT-CT camera with low-energy, highresolution collimators was used (GE Discovery NM/CT 670). A total of 60 pair views, each of 20-second duration, were acquired over 360 • , in a 128 × 128 matrix. The SPECT-CT data were reconstructed using ordered 3-dimensional subset expectation maximization (OSEM-3D) with 2 iterations, 16 subsets, and a Butterworth filter (GE Xeleris Functional imaging workstation; GE Healthcare, Chicago, IL) [1][2][3]14], The percentage uptake on the left lobe of total liver was calculated from both SPECT-CT data by OsiriX software (Geneva, Switzerland) and the 2 anterior and posterior planar views by using the geometrical mean method.

Findings
A large photopenic area in the right lobe of the liver was observed, attributed to necrosis resulting from the Y90 treatment, with minimal uptake in the remaining areas of the right lobe. Conversely, the left lobe experienced liver hypertrophy (Fig. 4a,b). By using the falciform ligament as a boundary, the percentage of left   lobe uptake to whole liver uptake was calculated at 87.1% (% left lobe uptake = left lobe uptake count / total liver uptake count x 100%).
Liver function tests remained within the normal range (Table 1); ICG was 20% after recheck. As the tumor occupied a large volume of a portion of the liver that was determined to be nonfunctioning, extended right hepatectomy was offered to the patient, with consideration of both benefits and risks of the procedure.
During the operation, the right lobe and segment 4 of the liver were visualized. Both were shrunken and fibrotic, with the tumor at the right lobe encroaching onto the right pedicle. Viable tumor was also visualized at the gallbladder bed and segment 4/5. An enlarged lymph node was identified at the porta region. The patient's albumin level was 26 g/L, in the week following surgery, however returned to 37 g/L one-month postsurgery (Table 1). No other complications were found.
Pathological analysis revealed a moderately differentiated HCC, stage pT3. The tumor was close to but not involving the capsular margin. The resection margin was negative for tumor, and the enlarged lymph node at the porta region did not contain metastatic tissue.
The patient was discharged on postoperative day 8 without complication and returned to the follow-up clinic one-month postoperation. He reported feeling well; had a fair appetite; no fever, wound, or other infection or disease; no weight loss or tea-colored urine; and walked unaided. The AFP was much reduced from 573 ng/mL to 14 ng/mL. Blood tests for liver function were normal demonstrating sustained functioning of the left liver lobe (Table 1).

Discussion
In this case study, a 15 × 10 x 13 cm HCC lesion was downstaged after Y90 radioembolization. However, the tumor remained viable prompting the consideration of lobectomy for this patient [15,16].
Liver volumetry by CT scan is commonly utilized prior to initiating liver segmentectomy or lobectomy. Yet, it can only offer a morphological volumetric assessment of the liver [17,18]. As seen in this patient, based on CT results, an FRV (47%) could not adequately reflect the physiological functioning of the remaining liver.
ICG-R-15 is an indicator of hepatic function that is often utilized prior to resection or transplantation [12]. However, it is difficult to determine functional liver reserve solely by ICG-R-15 as test results may be altered by regional hepatic blood flow and bilirubin levels [12]. In this patient, an ICG-R-15 of 22% caused the surgeons to reconsider the patient's eligibility for surgery. Therefore, we introduced the Tc-99 m SC SPECT-CT scan as an alternative assessment tool.
Fusion images from the SPECT-CT system offered better localization and differentiation on the physiological uptake, with actual functional anatomy shown (Fig. 4a,b). The images were reconstructed using OSEM-3D with CT-based attenuation correction. As a result, the percentage of the segmental or lobar liver function to the whole liver function could be accurately calculated (% of segmental or lobar liver function = segmental or lobar uptake count / the whole liver uptake count x 100%).
In this case, the hypertrophic left lobe reported 87.1% of the whole liver function. A finding that encouraged our team to proceed with extensive right hepatectomy.
Although segmental liver function can be easily assessed by Tc-99 m SC SPECT-CT, motion artifacts must be carefully observed. Patient positioning and respiratory motion will cause misregistration on the resulting images. Advanced software algorithms can be used for motion correction in image co-registration of the abdomen and thorax in order to minimize artifacts from respiratory motion. Patient cooperation is also important, as it plays a key role in producing reliable and precise results, and can be aided by prior, clear physician-patient communication [19].

Conclusion
Tc-99 m SC SPECT-CT imaging may offer a physiological imaging method that overcomes the limitation of the morphological CT scan, as this simple, noninvasive procedure can evaluate segmental liver function. By combining information with ICG-R-15, Tc-99 m SC SPECT-CT imaging may serve as a useful tool in the planning of precise segmentectomy and an accurate preoperative predictor for functional liver reserve.

Funding
We have no funding received for this study.

Ethical approval
Ethnical approval is issued by the Kowloon West Cluster Research Ethics Committee (KWC-Rec) Hong Kong Hospital Authority.

Consent
Written informed consent was obtained from patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the Editor in-Chief of this journal on request.

Author contribution
YeeMei Chan: Study concept, design, data collection, data analysis, interpretation and writing the paper.
WingHang Luk: Study concept, design, data collection, data analysis, interpretation and writing the paper.
LikFai Cheng: data interpretation and advisor. HoFung Chan: data interpretation and advisor. NY Pan: data interpretation and advisor. KaFai Ma: data interpretation and advisor.

Registration of research studies
Research Registry UIN: researchregistry4922.

Guarantor
YeeMei Chan and WingHang Luk are assigned as the guarantors for this study.

Provenance and peer review
Not commissioned, externally peer-reviewed.

Declaration of Competing Interest
We have no conflicts of interest or financial ties to any person or organisation.