Hepatocellular carcinoma (HCC) is a common cancer, and its treatment is difficult. A locoregional treatment may be proposed to certain patients, involving either chemoembolization or radioembolization. For radioembolization, 131I-lipiodol has been used for many years with good results [
Recently, radioembolization using microspheres labeled with yttrium-90 has been developed, notably TheraSphere (MDS Nordion, Ottawa, Canada) [
The activity to be injected (
A precise calculation of the vascularized volume is essential for dosimetric calculation, including the activity to be administered.
The vascularized or functional liver volume may also be analyzed using a vascular tracer such as human albumin serum labeled with technetium-99m (99mTc-MAA): the volume of distribution of 99mTc-MAA following selective injection into the hepatic artery, at the same position where the microspheres are to be injected, reflects the vascularized volume of the lobe to be treated.
In the absence of anatomical vascular variations, the definition of the vascularized liver volume is relatively easy to assess using CT. Contrarily, this calculation is much more problematic in the event of anatomical variations, such as when three distinct arterial branches vascularize the liver, a situation encountered in about 10% to 30% of patients [
SPECT has already been employed for calculating functional volumes [
While the use of SPECT/CT has not yet been reported in this setting, SPECT/CT-fused images may be helpful in delineating volumes, which may prove to be a reliable measurement of functional volumes. SPECT/CT may also be used to measure the tumor volume and nontumoral injected liver volume in order to calculate the doses absorbed by the tumor and the nontumoral liver, respectively.
In this paper, we report on a phantom study aimed at validating volume measurements based on SPECT/CT. We also stress the advantages of SPECT/CT in computing the vascularized liver volume in addition to calculating the doses absorbed by the healthy liver and tumor in a patient with complex hepatic vascularization.
We carried out a study on phantoms in order to validate the volume measurements performed using SPECT/CT. Various phantoms were used, including a cylindrical Jaszack phantom with a volume of 6,716 mL (cylinder 1) and two cylindrical phantoms of 774 (cylinder 2) and 473 mL (cylinder 3) for the measurement of large volumes (mimicking the liver). Spheres 1, 2, 3, and 4 of 55, 20.5, 16, and 8 mL, respectively, were used and inserted into the Jaszack phantom for measuring small representative tumor volumes. The activities of 99mTc used for phantoms representative of the liver (cylinder 1, 2, and 3) ranged from 55 to 170 MBq. For the spheres, activities of 18.5, 37, 55.5, and 74 MBq were used. These activities were chosen in order to simulate standard clinical situations involving an injection of 185 MBq of 99mTc-MAA in a liver of 1500 mL, with tumor uptake of 10%, 20%, 30%, and 40% of the injected activities, respectively.
SPECT/CT acquisitions were performed (32 projections, 180°,
Volume measurement was carried out on SPECT and SPECT/CT images using a Syngo data-processing console display unit (Siemens) with “Volume Analysis” software. This software allowed us to generate semi-automatically the volume-of-interest (VOI) in the liver and tumor by means of an isocontour definition method. Each voxel with an activity reaching or exceeding a threshold percentage of the highest activity was included in the VOI.
For each volume measurement, the isocontour was fitted by superposition on either the contour of the hot spot located by SPECT alone or the internal wall of the phantom located on the SPECT/CT fusion images (Figure
Delineation of VOIs used for quantitative analysis of SPECT and SPECT/CT analysis (a, b): VOI defined on SPECT hot spot alone. Fused SPECT/CT image with the VOI matching with the hot spot ((a), SPECT/CT scale); CT scale showing that the VOI is not accurate and larger than the sphere (b). (c): VOI defined with SPECT/CT and using the CT scale: the isocontour was fitted by superposition on the boundaries of the internal wall of the sphere.
Measurements of volumes by SPECT and SPECT/CT were carried out by two operators blinded to the phantom volumes.
For each method, the percentage of error was calculated by reference to the actual volume of the phantoms. The interobserver reproducibility was evaluated using the Bland-Altman test of agreement, with values ≥0.8 considered to be excellent, values in the range of 0.6–0.8 to be good, values in the range of 0.4–0.6 to be poor, and values <0.4 to be very poor.
We report on the case of a 63-year-old patient with a voluminous HCC infiltrating the whole left liver (Figure
case report: patient with a large HCC Contrast enhanced CT evidencing a large infiltrative tumor of the left liver (a) with a portal vein thrombosis (b).
At the end of the diagnostic angiography, 185 MBq of 99mTc-MAA was injected selectively for SPECT/CT. The parameters of acquisition and reconstruction were the same as those used for the phantom study. SPECT/CT quantitative analysis (volume and count measurements) was conducted on the fusion images. For each VOI, the threshold value was adjusted so that the isocontours of the distribution volume of MAA were superimposed on the fusion images that corresponded to the contours of the liver and tumor (Figure
Case report: delineation of the tumoral and injected lover VOI on SPECT/CT whole; injected liver VOI with SPECT/CT color scale (a), whole injected liver VOI with CT scale and visualisation of SPECT isocontour (b), tumoral VOI with SPECT/CT color scale (c) and tumoral VOI with CT scale and visualisation of SPECT isocontour (d).
The dose absorbed by the tumor was calculated based on the standard formula as follows:
The dose absorbed by the healthy injected liver was calculated based on the standard formula as follows:
The Therasphere injection was administered 8 days later during the second angiography, with the aim to administer a dose of 120 ± 20 Gy to the vascularized volume.
In total, acquisitions and measurements were carried out on 23 test objects of different configuration (size and activity), with results for both operators provided in Tables
Operator 1 results.
Phantom configuration | True sphere/ | SPECT alone | SPECT- CT | |||||
Isocontour (%) | Measured volume (cm3) | Error (%) | Isocontour (%) | Measured volume (cm3) | Error Vol. (%) | |||
18,5 MBq/sphere | Cylinder 1 | — | 2% | 6521 | −2,90 | 2% | 6521 | −2,90 |
Sphere 1 | 2.8 | 42% | 75,45 | 37,18 | 48% | 57,22 | 4,04 | |
Sphere 2 | 7.6 | 31% | 22,35 | 6,43 | 27% | 27,08 | 28,95 | |
Sphere 3 | 9.6 | 27% | 18 | 12,50 | 29% | 16,94 | 5,88 | |
Sphere 4 | 19.6 | 15% | 14,72 | 84,00 | 19% | 10,91 | 36,38 | |
37 MBq/sphere | Cylinder 1 | — | 2% | 6180 | −7,98 | 1% | 6735 | 0,28 |
Sphere 1 | 6 | 46% | 44,86 | −18,44 | 42% | 49,06 | −10,80 | |
Sphere 2 | 17 | 25% | 22,58 | 7,52 | 29% | 20,52 | −2,29 | |
Sphere 3 | 23.4 | 23% | 17,55 | 9,69 | 27% | 14,95 | −6,56 | |
Sphere 4 | 43.8 | 31% | 10,45 | 30,63 | 35% | 9,08 | 13,50 | |
55,5 MBq/sphere | Cylinder 1 | — | 1% | 6737 | 0,31 | 1% | 6737 | 0,31 |
Sphere 1 | 9.9 | 44% | 45,32 | −17,60 | 31% | 59,28 | 7,78 | |
Sphere 2 | 29.6 | 33% | 18,62 | −11,33 | 31% | 19,3 | −8,10 | |
Sphere 3 | 38.6 | 33% | 17,32 | 8,25 | 35% | 16,17 | 1,06 | |
Sphere 4 | 73.1 | 31% | 14,37 | 79,63 | 40% | 10,53 | 31,63 | |
74 MBq/sphere | Cylinder 1 | — | NA | NA | NA | NA | NA | NA |
Sphere 1 | 16 | 52% | 33,72 | −38,69 | 31% | 54,86 | −0,25 | |
Sphere 2 | 45 | 21% | 23,5 | 11,90 | 27% | 19,81 | −5,67 | |
Sphere 3 | 57 | 21% | 18,05 | 12,81 | 27% | 15,49 | −3,19 | |
Sphere 4 | 114 | 31% | 5,95 | −25,63 | 21% | 8,32 | 4,00 | |
55 MBq | Cylinder 2 | — | 46% | 709 | −8,40 | 25% | 795 | 2,71 |
116 MBq | Cylinder 2 | — | 46% | 667 | −13,82 | 35% | 770 | −0,52 |
72 MBq | Cylinder 3 | — | 33% | 455 | −3,81 | 23% | 515 | 8,88 |
Opertor 2 results.
Phantom configuration | True sphere/ | SPECT alone | SPECT-CT | |||||
Isocontour (%) | Measured volume (cm3) | Error (%) | Isocontour (%) | Measured volume (cm3) | Error (%) | |||
18,5 MBq/sphere | Cylinder 1 | — | 1% | 7087 | 5,52 | 2% | 6521 | −2,90 |
Sphere 1 | 2.8 | 31% | 207 | 276,36 | 48% | 57,2 | 4,00 | |
Sphere 2 | 7.6 | 13% | 104,5 | 397,62 | 28% | 24,4 | 16,19 | |
Sphere 3 | 9.6 | 19% | 27,4 | 71,25 | 29% | 16,9 | 5,62 | |
Sphere 4 | 19.6 | 8% | 29,2 | 265,00 | 19% | 10,9 | 36,25 | |
37 MBq/sphere | Cylinder 1 | — | 2% | 6180 | −7,98 | 1% | 6700 | −0,24 |
Sphere 1 | 6 | 7% | 169,7 | 208,55 | 34% | 53,56 | −2,62 | |
Sphere 2 | 17 | 3% | 113,7 | 441,43 | 23% | 24,34 | 15,90 | |
Sphere 3 | 23.4 | 3% | 119,78 | 648,63 | 27% | 14,9 | −6,88 | |
Sphere 4 | 43.8 | 4% | 53,48 | 568,50 | 33% | 9,8 | 22,50 | |
55,5 MBq/sphere | Cylinder 1 | — | 1% | 6737 | 0,31 | 1% | 6737 | 0,31 |
Sphere 1 | 9.9 | 10% | 159,3 | 189,64 | 35% | 55,7 | 1,27 | |
Sphere 2 | 29.6 | 4% | 85 | 304,76 | 25% | 22,7 | 8,10 | |
Sphere 3 | 38.6 | 7% | 51,5 | 221,88 | 36% | 15,5 | −3,13 | |
Sphere 4 | 73.1 | 6% | 44,1 | 451,25 | 36% | 12 | 50,00 | |
74 MBq/sphere | Cylinder 1 | — | 1% | 6565 | −2,10 | 1 | 6565 | −2,10 |
Sphere 1 | 16 | 15% | 99,5 | 80,91 | 32% | 56 | 1,82 | |
Sphere 2 | 45 | 6% | 54,1 | 157,62 | 23% | 23,7 | 12,86 | |
Sphere 3 | 57 | 5% | 42,8 | 167,50 | 25% | 17,4 | 8,75 | |
Sphere 4 | 114 | 2% | 35,8 | 347,50 | 20% | 8,7 | 8,75 | |
55 MBq | Cylinder 2 | — | 17% | 887 | 14,60 | 27% | 801 | 3,49 |
116 MBq | Cylinder 2 | — | 19% | 855 | 10,47 | 29% | 775 | 0,13 |
72 MBq | Cylinder 3 | — | 21% | 520 | 9,94 | 27% | 481 | 1,69 |
For SPECT alone, mean errors of volume measurements were relatively high (>20%, Table
Mean error (±1 standard deviation) with SPECT and SPECT/CT volume measurements.
SPECT alone | SPECT/CT | |||||
All volumes | volumes ≥16 mL | volumes ≥473 mL | All volumes | volumes ≥16 mL | volumes ≥473 mL | |
Operator 1 | 20.4 ± 22.4% | 12.8 ± 10.3% | 6.2 ± 4.8% | 8.5 ± 10.5% | 5.6 ± 6.7% | 2.2 ± 3.1% |
Operator 2 | 210.8 ± 194.5% | 169.3 ± 181.3% | 7.2 ± 4.9% | 9.4 ± 12.3% | 5.2 ± 5.1% | 1.5 ± 1.3% |
Interobserver reproducibility was inadequate with SPECT alone, as the Bland-Altman test result was only 0.2.
For SPECT/CT, results were superior, as mean errors of measurement were <10% for the two operators, being <6% for the measurement of volumes ≥16 cm3 and even <2.5% for volumes ≥473 mL (Table
Diagnostic angiography revealed an anatomical variant with three arterial branches vascularizing the liver: a right hepatic artery originating from the mesenteric artery (Figure
Case report: angiographic and scintigraphic data; right selective angiography (a), selective angiography of the common hepatic artery vascularizing segment IV and the left liver (b), SPECT (c) and SPECT/CT (d) after injection of the MAA at the level of the central hepatic artery revealing an unexpected uptake in the right liver, in addition to the expected uptake of segment IV and left liver (whole liver distribution, volume 1829cc).
Unexpectedly, after injecting MAA into the common hepatic branch, SPECT/CT revealed the whole liver distribution of the MAA (Figure
After injecting contrast or MAA into the common hepatic branch, the vascularized liver volume was only 346 mL based on angiographic + CT data versus 1829 mL with quantitative MAA SPECT. Moreover, the tumoral uptake calculated using quantitative MAA SPECT data represented 69.1% of the total liver uptake with no lung shunting apparent.
Based on angiographic + CT, the activity of 90Y-loaded microspheres to be injected in order to obtain a dose of 120 Gy in the injected volume, presumed to be only the left liver, would have been 0.8 GBq.
Based on quantitative MAA SPECT analysis, a 5 GBq activity was planned to be used, resulting in a dose of 132 Gy to the vascularized liver (whole liver), a tumoral dose of 275 Gy, and a nontumoral injected liver dose of only 57 Gy.
Based on quantitative MAA SPECT/CT analysis instead of standard angiographic and CT data, the patient was treated with 5 GBq Therasphere. No toxicity was observed, and a major response was achieved (Figure
Case report: follow-up CT scan 4 months after injection of 5 GBq of in the central branch: major response.
SPECT is currently used to define functional volumes of different organs such as the liver [
We describe a new method of organ and tumor volume calculation based on SPECT/CT data using simple manufactured software. This adaptive thresholding method was based on a direct visualization of tumoral and liver boundaries on SPECT/CT images, avoiding the use of thresholds dependent on predefined values. We showed that SPECT alone (visual delimitation of the volume based on the hot spot) was acceptable for large volumes (error <10% for volumes >473 mL), but inaccurate for small volume measurements, in line with previously published literature. In fact, visual volume definition is highly dependent on the individual investigator and display window setting (type of grey or color window and saturation used), potentially leading to large volume over- or underestimation [
The case reported in our study clearly demonstrates that in patients with anatomical abnormalities in liver vascularization, MAA SPECT/CT vascularized volume measurement is a more functional and reliable method than volume calculations using the anatomical Couinaud segmentation based on angiographic and CT data. In our case report, due to MAA SPECT/CT, we were able to detect an unexpectedly large volume of liver slightly vascularized after selective injection of MAA into the common hepatic branch. This method revealed the existence of microvascular communications between different anatomic segments, probably via intratumoral arterioportal shunts with low arterial blood flow, which were not visible on angiography but detected using MAA SPECT/CT.
The therapeutic impact for our patient was crucial, since it led us to significantly increase the activity injected for treatment, 5 GBq instead of 0.8 GBq, without any toxicity but an excellent response.
Furthermore, the evaluation of tumor and healthy liver doses based on the quantitative analysis of SPECT/CT is of great interest. In fact, the dose absorbed by the tumor represents the parameter most likely to correlate with response. This parameter depends directly on the quantity of radioactivity fixed in the tumor (i.e., degree of vascularization) as well as the total quantity of microspheres injected. Only MAA SPECT/CT allows us to evaluate this parameter, which corresponds to the tumoral absorbed dose.
The effectiveness and reproducibility of MAA SPECT/CT volume measurements was confirmed by a phantom study, with a mean error <6% for volumes ≥16 mL and <2.5% for larger volumes, such as the whole liver. MAA SPECT/CT appears to be a more functional tool in identifying and calculating vascularized liver volumes than angiography, as it is able to identify unexpected vascularized areas with low blood flow not recognizable by angiography. In addition, quantitative MAA SPECT/CT allows for calculating the tumoral absorbed and nontumoral injected liver doses. Therefore, quantitative MAA SPECT/CT may be of great help in defining vascularized liver volumes and calculating the activity to be administered, especially in patients with complex hepatic vascularization. Quantitative MAA SPECT/CT may be instrumental in optimizing the activity to be injected, thereby increasing the therapeutic effectiveness. Nonetheless, this hypothesis must still be validated in controlled studies.
E. Garin is a consultant for Nordion.