Clinical Application of Technetium-99m-Labeled Red Blood Cells Subcutaneous Radionuclide Venography and Abdominal/Pelvic Hybrid SPECT/CT Imaging in Patients with Suspicion of Proximal Deep Vein Thrombosis

Technetium-99m-labeled red blood cells subcutaneous radionuclide venography can apply to evaluate deep venous flow of lower extremities. We introduce additional abdominal/pelvic hybrid SPECT/CT (single-photon emission computed tomography with computed tomography) to scrutinize the proximal deep venous flow defects in the iliac vein. SPECT/CT imaging is collected when disturbed or asymmetrical iliac venous flow is noted on the planar imaging of Tc-99m-labeled red blood cells subcutaneous radionuclide venography. The region of SPECT/CT imaging includes abdominal aorta, inferior vena cava and bilateral iliac vessels. We present three cases with suspicion of deep vein thrombosis in the iliac vein. Tc-99m-labeled red blood cells subcutaneous radionuclide venography with SPECT/CT revealed not only provides us the venous flow but also other information including abnormal vessel structure, space-occupying lesion and abnormality in other organs. In conclusion, if disturbed or asymmetrical iliac venous flow and abnormal collateral venous drainage in the abdomen are noted on the Tc-99mlabeled red blood cells subcutaneous radionuclide venography, SPECT/CT imaging may arrange for further information and differential diagnosis of lower extremities swelling; not only in detecting deep vein thrombosis.


Introduction
There are many methods to complete radionuclide venography in the nuclear medicine department, including Technetium-99m MAA (Tc-99m macro aggregated albumin) radionuclide venography and Technetium-99m-labeled red blood cells subcutaneous radionuclide venography. Tc-99m-labeled red blood cells subcutaneous radionuclide venography using Tc-99m in vivo tagged red blood cells is an alternative procedure for conventional intravenous radionuclide venography [1,2]. In our hospital, we use in vivo labeling method. First of all, we inject stannous pyrophosphate with normal saline through intravenous route. About 15 min later, the patient is placed on the examination table in the supine position and we inject the dose of 6 mCi Tc-99m pertechnetate per limb via subcutaneous route between big toe and second toe on bilateral dorsum of foot ( Figure 1A). By reduction of stannous pyrophosphate, Tc-99m can bind to red blood cells.
The early deep venous blood flow image is collected by means of tourniquets for compression of superficial venous drainage ( Figure  1B). Half-body image from bilateral foot to dome of liver is acquired with low energy high-resolution collimator and at acquisition speeds of 18 cm/min. The injection site was not included due to scattering artifact. The blood-pool half-body image is collected without tourniquets. Image is acquired at acquisition speeds of 20 cm/min. Single-photon emission computed tomography with computed tomography (SPECT/CT) imaging is arranged when proximal deep venous flow defects in the iliac vein are noted. The region of SPECT/CT imaging includes abdominal aorta, inferior vena cava and bilateral iliac vessels. The SPECT images setting are 32 projection angles and 30 second/angle. CT protocol consists of 1-mm-thick slices with tube voltage of 120 kV and tube current setting of 30 mA.
SPECT is reconstructed using iterative methods with a matrix size of 64 × 64. This reconstruction of CT is done with iterative reconstruction algorithms. We analyze the functional data from SPECT imaging with anatomical localization from CT imaging.

Case 1
A 61-year-old male patient with past histories of diabetes mellitus, hypertension, old stroke without sequelae. One-day history of swelling in his right lower extremity. Tc-99m labeled red blood cells subcutaneous radionuclide venography was performed under suspicion of deep vein thrombosis. Irregular and interruption of deep venous flow were noted in the right lower extremity under tourniquets use. After tourniquets were removed, collateral vessels were noted in the right lower extremity ( Figure 2). Lower extremity venous ultrasonography images proved deep vein thrombosis in the right femoral vein and knee ( Figure 3). SPECT/CT imaging was performed for disturbed venous flow in the right iliac vein and revealed iliac venous engorgement with a hypodense lesion in the right iliac vein ( Figure 4).

Discussion
Many patients are referred to our nuclear medicine department for suspicion of deep vein thrombosis. Intravenous radionuclide venography and radiographic contrast venography need intravenous administration. However, it is difficult to find a venous route from limb swelling. Thus, it is much easier to inject radiopharmaceutical via subcutaneous route.
Contrast venography has long been considered the reference test for the diagnosis of deep vein thrombosis. Due to other noninvasive tests, the need for contrast venography reduced. Contrast venography could not be performed in some patients due to contraindications or technical factors. Some possible risks of contrast venography included an allergic reaction to contrast material or a risk of injury to the kidneys in patients with impaired renal function. Compression ultrasonography has some limitations include not detect isolated thrombi in the iliac vein or that portion of the femoral vein within the adductor canal and pelvic neoplasms or abscesses may demonstrate isolated noncompressibility of the femoral vein when thrombosis is absent [3,4]. The benefit of ultrasonography is no radiation exposure. Due to above reasons, Tc-99m-labeled red blood cells subcutaneous radionuclide venography plays a role in this situation.
However, some patients may have an allergic reaction to stannous pyrophosphate. We should monitor patients' condition after stannous pyrophosphate injection. The radiation dose to the skin at the site of subcutaneous injection is approximately 0.02 Gy/mCi according to previous study [2]. The dose-length product of SPECT/CT imaging in the abdomen/pelvis is less than that of contrast venography and contrast venography with higher effective dose.
Tc-99m-labeled red blood cells subcutaneous radionuclide venography with SPECT/CT provides us not only the venous flow in the iliac veins but also other information including abnormal vessel structure, space-occupying lesion and abnormality in other organs. May-Thurner syndrome is disease with abnormal vessel structure of the left common iliac vein stenosis secondary to compression of the left common iliac vein between the right common iliac artery and the underlying vertebral body [5]. If a patient with suspected May-Thurner syndrome on the SPECT/CT imaging, further imaging survey and treatments will be suggested. In our clinical experience, additional SPECT/CT imaging revealed psoas muscle abscess or deep vein thrombosis with hydroureter in a patient with a past history of colon cancer. These information may assist physicians in clinical treatment or assess the possible recurrence of colon cancer. Thus, Tc-99m-labeled red blood cells subcutaneous radionuclide venography with SPECT/CT provides the differential diagnosis of swelling in the lower extremities.
In conclusion, Tc-99m-labeled red blood cells subcutaneous radionuclide venography is a convenient method to evaluate the deep venous flow when patients have limb swelling. If disturbed or asymmetrical iliac venous flow and abnormal collateral venous drainage in the abdomen are noted on the Tc-99m-labeled red blood cells subcutaneous radionuclide venography, SPECT/CT imaging may arrange for further information such as abdominal and pelvic mass lesions [6]. Compression ultrasonography and Tc-99m-labeled red blood cells subcutaneous radionuclide venography with SPECT/CT imaging might play a complementary role in detecting deep vein thrombosis.