Diagnosis and Whole Body Screening Using Blood Pool Scintigraphy for Evaluating Congenital Vascular Malformations Young Hwan Kim,1,2 Joon Young Choi,2 Young-Wook Kim,3 Dong-Ik Kim,3 Young Soo Do,4 Yearn Seong Choe,2 Kyung-Han Lee,2 and Byung-Tae Kim,2 Guri-si and Seoul, Korea
Background: Because magnetic resonance imaging and angiography are inappropriate for whole-body screening because of high cost or invasiveness, we investigated the potential of whole-body blood pool scintigraphy (WBBPS) as a screening and diagnostic tool for congenital vascular malformations (CVMs). Methods: The subjects of the study were 137 patients (mean age: 20 ± 16 years; range: 0.3e68 years) with suspected CVM. Whole-body anterior and posterior images were acquired twenty minutes after injection of 760 MBq 99mTc-labeled red blood cells (pediatric dose: 13 MBq/kg). The final diagnosis was determined by clinical findings, magnetic resonance imaging, angiography, Doppler sonography, and lymphoscintigraphy. Results: Of these patients, 124 had venous malformations, and 13 had lymphatic malformations. WBBPS successfully detected abnormal blood pooling lesions in 96.8% (120/124) of the patients with venous malformations. None of the patients with lymphatic malformation showed abnormal uptake on WBBPS. In addition, WBBPS detected 41 additional abnormal vascular lesions that were not found during initial clinical evaluation in 16.9% (21/124) of the patients with venous malformations. Conclusion: WBBPS is a valuable diagnostic and screening modality for the initial evaluation of CVM because of its high characterizing accuracy of 97.1% and the ability to image the whole body.
INTRODUCTION Supported by the research fund of Hanyang University (HY-2011-N). 1 Department of Nuclear Medicine, Hanyang University Guri Hospital, Hanyang University School of Medicine, Guri-si, Gyeonggido, Korea. 2
Department of Nuclear Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. 3 Division of Vascular Surgery, Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. 4 Department of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Correspondence to: Joon Young Choi, MD, PhD, Department of Nuclear Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong, Gangnam-gu, Seoul 135-710, Korea; E-mail: [email protected] Ann Vasc Surg 2014; 28: 673–678 http://dx.doi.org/10.1016/j.avsg.2013.02.025 Ó 2014 Published by Elsevier Inc. Manuscript received: October 11, 2012; manuscript accepted: February 12, 2013; published online: December 2, 2013.
Congenital vascular malformation (CVM) is one of the most difficult conditions to diagnose and treat.1 Its clinical presentation is extremely variable, ranging from an asymptomatic birthmark to a lifethreatening condition. This variation is a major challenge for even the most experienced clinicians.2,3 The accurate diagnosis and classification of patients with CVM is therefore important. Based on the predominant component of the vascular defect, CVMs are classified into arterial, venous, lymphatic, arteriovenous shunting, combined (mostly hemolymphatic), or capillary types.4e6 Classification is essential, because the treatment and prognosis of CVMs differ according to type. Even though traditional arteriography and phlebography remain the criterion standards for determining CVM type, they are too invasive to be diagnostic or screening tools for CVM. Therefore, 673
674 Kim et al.
Annals of Vascular Surgery
many noninvasive diagnostic modalities have been developed.3 Of these modalities, magnetic resonance imaging (MRI) and duplex ultrasonography have become the most used, not only for initial diagnosis but also for assessing the results of treatment with multisession therapy.7,8 MRI usually provides conclusive evidence for proper differentiation between venous malformation (VM), lymphatic malformation (LM), and hemangioma, and is excellent for characterizing and discriminating the extent of vascular lesions. It is becoming the criterion standard for CVM diagnosis, replacing the classic role played by angiography.9 Both MRI and duplex ultrasonography have some limitations as techniques for CVM diagnosis and management. Using MRI for whole-body screening for additional lesions and for frequent follow-up assessment is costly,6,10 and duplex ultrasonography is limited in its ability to detect deep lesions and lesions adjacent to air or bone.6,11 An alternative method for the diagnosis and management of CVM is whole-body blood pool scintigraphy (WBBPS) using 99mTc-labeled red blood cells (RBCs). This method is based on the principle of gated blood-pool radionuclide ventriculography. It was first adopted as a supplementary test to reinforce modalities such as ultrasonography, MRI, and angiography, and has been used extensively at our institute for several years.10,12 Currently, WBBPS is used not only as an initial diagnostic test for CVM, but also as a follow-up test, because it has several advantages over the established techniques of CT, MRI, and angiography, including safety, noninvasiveness, and low cost.10,13e15 In addition, it has the potential to detect additional vascular lesions because of its whole body scanning capability. Therefore, in this study, we investigated the role of WBBPS as a diagnostic and whole-body screening tool for CVM.
erythrocyte labeling method. Stannous medronate was injected intravenously; then, after 15 minutes, 5 mL of blood was withdrawn into a syringe containing anticoagulant (ACD-A). The erythrocytes in this sample were labeled with 760 MBq/kg (for adults) or 13 MBq/kg (for children) of 99mTc. The labeling efficiency was >90% in all cases. The radiolabeled erythrocytes were then injected back into the patient. Whole-body imaging was performed 20 min after injection of the radiolabeled erythrocytes.10
METHODS
Of the 137 patients studied, 124 proved to have VMs (87 in the extremities, 25 in the head and neck, and 12 in the trunk). The remaining 13 patients were diagnosed with LMs. WBBPS had a high sensitivity of 96.8% (120/124) for the diagnosis of VMs by the presence of abnormal blood pooling lesions. Figure 1 shows a representative WBBPS result for VMs. The 4 patients with VMs who were found to be negative by WBBPS had very small vascular lesions. However, abnormal blood pool uptake was not observed by WBBPS in any of the 13 patients with LMs, giving a 100% specificity for diagnosis of VMs. Figure 2 shows a representative result of a WBBPS and a lymphoscintigram positive for LM. Therefore, WBBPS had an accuracy of
Subjects The subjects of this study were 137 consecutive patients with suspected CVM. The mean age of the patients was 20 ± 16 years (range: 0.3e68 years). Sixty-three patients were men, and 74 were women. All patients underwent 99mTc-RBC WBBPS at Samsung Medical Center, Seoul, Korea. Whole-Body Blood Pool Scintigraphy A dual-head gamma camera (Biad; Trionix Research Laboratory, Twinsburg, OH) was used for WBBPS. Erythrocytes were labeled by a modified in vivo
Analysis Scintigraphic results were interpreted by the consensus of 2 nuclear medicine physicians. Abnormally asymmetric blood pool lesions were considered to be a blood pooling CVM, such as a VM. If there was no significant abnormal blood pooling lesion, the clinically suspected lesion was considered to be a noneblood pooling CVM, such as an LM or other pathologic lesion. When abnormal focal blood pooling lesions were detected at locations other than the clinically suspected sites, additional diagnostic work-up was recommended. The final diagnosis was determined by clinical assessment of clinical findings, regional MRI (n ¼ 137), angiography (n ¼ 92), and Doppler ultrasonography (n ¼ 94). Twenty-eight patients with suspected LMs on initial study underwent additional radionuclide lymphoscintigraphy. Ethics The institutional review board of Samsung Medical Center approved this retrospective study protocol, and informed consent was waived.
RESULTS
Vol. 28, No. 3, April 2014
Blood pool scintigraphy for evaluating CVM 675
Fig. 1. (A) Whole-body blood pool scintigraphy (WBBPS) and (B) magnetic resonance imaging (MRI) scans of a 10-year-old female with a vascular malformation in the left lower leg. The WBBPS image reveals
abnormal increased blood pooling, indicative of a lesion in the left proximal calf area, and the T2-weighted coronal MRI image reveals a mass with high signal intensity involving the left soleus muscle.
Fig. 2. (A) Whole-body blood pool scintigraphy (WBBPS) and (B) lymphoscintigraphy images of a 45-year-old woman with a lymphatic malformation in the left lower extremity. The WBBPS image shows no significant
abnormal blood pooling, indicating the absence of lesions. In contrast, the lymphoscintigraphy scan shows abnormal accumulation of radioactivity in the left lower leg without visualization of the left main epifascial lymphatic vessels.
97.1% for characterizing CVMs. There was no difference between the 2 interpreters in terms of the presence of abnormal blood pooling lesions. WBBPS detected 41 additional abnormal vascular lesions not found in the initial clinical evaluation, and these were present in 16.9% (21/124) of the patients with a VM (Figs. 3 and 4). Additional assessment techniques, such as MRI or angiography, were performed
on 17 of the 41 abnormal vascular lesions (41.5%), and 14 lesions (82.4%) were proven to be VMs.
DISCUSSION Recently, advances in the diagnosis and management of CVMs have been made because of the establishment of the Hamburg classification (1988),4,16
676 Kim et al.
Fig. 3. (A and B) Whole-body blood pool scintigraphy image of a 22-year-old woman with a congenital vascular malformation in the right cheek area showing abnormal blood pooling indicative of additional clinically unsuspected vascular lesions in the right jugular, right upper back, left lower back, and right calf areas (black arrows).
which provides etiologic, anatomic, and pathophysiologic information on various kinds of CVMs.9 Other advances have been the development of various noninvasive vascular diagnostic tests (e.g.,
Annals of Vascular Surgery
MRI, duplex ultrasonography, WBBPS, transarterial lung perfusion scintigraphy, computed tomography with angiocontrast enhancement, lymphoscintigraphy, ultrasonographic lymphangiography, magnetic resonance lymphangiography, volumetry, and air plethysmography), which are able to provide sufficient information for the accurate diagnosis of various forms of CVMs.7,17,18 MRI in particular is excellent for the accurate characterization of CVMs, especially in the limbs, and the anatomic extent, degree of cellularity, and flow characteristics can be readily gauged. In addition, because it is noninvasive and provides the same basic information as angiography, it can serve as the primary diagnostic test for suspected CVM, particularly in infants and children.8,9 Because of its high cost and limited coverage, it is not suitable for routine whole-body screening. In Korea, regional MRI costs 3 times more than WBBPS. In addition, because MRI is not a whole-body scanning modality, it can only detect lesion in the area on which the MRI is focused, and may not detect any additional sites of CVM throughout the body. In this study, we assessed the use of WBBPS for CVM diagnosis and screening. This technique was previously known as multigated acquisition scanning for cardiac evaluation, but has recently been used in the area of CVM diagnosis and management. In this study, WBBPS was able to diagnose VMs in 120 of a total of 124 patients (sensitivity: 96.8%), showing it to be a highly dependable and sensitive diagnostic method. There were 4 false negative cases in which the lesions were too small to be detected, but this was easily compensated for by other complementary noninvasive tests, such as MRI and duplex ultrasonography. In addition, there was no abnormal blood pooling in any patients with LM. The differential diagnosis between VM and LM is clinically important, because the primary treatment modality is different. For VM, absolute ethanol treatment is used, while sclerotherapy with other agents, such as doxycycline or physical therapy for combined lymphedema, are the main treatment methods for LMs.17,19e22 Although MRI is the most commonly used method of diagnosis for various CVMs, MRI is limited in its ability to differentiate between low-flow type CVMs, such as VMs and LMs.15,23 Considering the high accuracy of WBBPS of 97.1% for characterizing low-flow CVMs, WBBPS may be useful for identifying which treatment is most appropriate for such lesions. This does not mean that MRI should be replaced by WBBPS for evaluating CVM. Regional MRI is still necessary for anatomic information and ruling out other possible diagnoses, such as vascular tumors.
Vol. 28, No. 3, April 2014
Blood pool scintigraphy for evaluating CVM 677
Fig. 4. (A) Whole-body blood pool scintigraphy image of a 2-year-old female with a vascular malformation in the right chest wall revealing abnormal blood pooling indicative of additional clinically unsuspected vascular lesions in the right buttock, back, and left ankle areas (black
arrows). (B) Follow-up T2 fat-suppressed magnetic resonance imaging scan revealing a high signal intensity lobulating mass involving both gluteus medius muscles (white arrows).
Therefore, WBBPS can be an additional diagnostic tool for evaluating CVM. WBBPS detected 41 additional abnormal vascular lesions in 21 patients that were not found in the initial evaluation. Although these lesions were asymptomatic and did not require immediate intervention, the ability to detect additional lesions is important because occult CVMs can grow during follow-up. Early detection allows clinicians to carefully evaluate these lesions during follow-up. Because of the retrospective study design, only 17 lesions could be studied further, and most of these were found to be VMs. WBBPS may provide useful information not only as a screen for previously undetected CVMs, but also as a follow-up test. Previous preliminary studies suggested that, during follow-up, WBBPS yielded not only qualitative image-based measurements of gross changes in the extent of abnormal blood pooling, but also quantitative measurements of the percentage reduction of 99mTc-labeled RBCs in regions of interest, which might permit more precise assessment of the success of treatment.7,19 In this study, because we focused only on the diagnostic and whole-body screening roles of WBBPS, we cannot provide data on the value of follow-up studies. Additional studies to clarify the role of WBBPS in the follow-up of CVM are warranted because of the limitations of previous studies, such as small numbers of subjects.
of its high accuracy, cost-effectiveness, noninvasiveness, and ability to image the whole body.
CONCLUSION WBBPS is a valuable diagnostic and screening modality for the initial evaluation of CVM because
REFERENCES 1. Szilagyi DE, Smith RF, Elliott JP, Hageman JH. Congenital arteriovenous anomalies of the limbs. Arch Surg 1976;111: 423e9. 2. Mulliken JB. Cutaneous vascular anomalies. Semin Vasc Surg 1993;6:204e18. 3. Rutherford RB. Congenital vascular malformations: diagnostic evaluation. Semin Vasc Surg 1993;6:225e32. 4. Belov S. Classification of congenital vascular defects. Int Angiol 1990;9:141e6. 5. Enjolras O. Classification and management of the various superficial vascular anomalies: hemangiomas and vascular malformations. J Dermatol 1997;24:701e10. 6. Kim YH, Choi JY, Kim YW, et al. Characterization of congenital vascular malformation in the extremities using whole body blood pool scintigraphy and lymphscintigraphy. Lymphology 2009;42:77e84. 7. Lee BB, Kim DI, Huh S, et al. New experiences with absolute ethanol sclerotherapy in the management of a complex form of congenital venous malformation. J Vasc Surg 2001;33: 764e72. 8. Pearce WH, Rutherford RB, Whitehill TA, Davis K. Nuclear magnetic resonance imaging: its diagnostic value in patients with congenital vascular malformations of the limbs. J Vasc Surg 1988;8:64e70. 9. Lee BB, Choe YH, Ahn JM, et al. The new role of magnetic resonance imaging in the contemporary diagnosis of venous malformation: can it replace angiography? J Am Coll Surg 2004;198:549e58. 10. Lee BB, Mattassi R, Kim BT, et al. Contemporary diagnosis and management of venous and arterio-venous shunting malformation by whole body blood pool scintigraphy. Int Angiol 2004;23:355e67. 11. Hyodoh H, Hori M, Akiba H, et al. Peripheral vascular malformations: imaging, treatment approaches, and therapeutic issues. Radiographics 2005;25(suppl 1):S159e71.
678 Kim et al.
12. Lee BB, Bergan J, Gloviczki P, et al. Diagnosis and treatment of venous malformations. Consensus document of the International Union of Phlebology (IUP)-2009. Int Angiol 2009;28:434e51. 13. Hardoff R, Gips S, Front A. Imaging patterns of vascular lesions of the head and neck demonstrated by Tc-99m labeled red blood cells. Clin Nucl Med 1992;17:288e91. 14. Inoue Y, Wakita S, Yoshikawa K, et al. Evaluation of flow characteristics of soft-tissue vascular malformations using technetium-99m labelled red blood cells. Eur J Nucl Med 1999;26:367e72. 15. Lee JY, Choi JY, Kim YH, et al. Characterization of congenital lymphatic and blood vascular malformations in the head and neck using blood pool scintigraphy and SPECT. Lymphology 2010;43:149e57. 16. Belov S. Anatomopathological classification of congenital vascular defects. Semin Vasc Surg 1993;6:219e24. 17. Lee BB. Advanced management of congenital vascular malformations (CVM). Int Angiol 2002;21:209e13.
Annals of Vascular Surgery
18. Lee BB, Bergan JJ. Advanced management of congenital vascular malformations: a multidisciplinary approach. Cardiovasc Surg 2002;10:523e33. 19. Lee BB, Do YS, Byun HS, et al. Advanced management of venous malformation with ethanol sclerotherapy: midterm results. J Vasc Surg 2003;37:533e8. 20. Burrows PE, Mitri RK, Alomari A, et al. Percutaneous sclerotherapy of lymphatic malformations with doxycycline. Lymphat Res Biol 2008;6:209e16. 21. Cordes BM, Seidel FG, Sulek M, et al. Doxycycline sclerotherapy as the primary treatment for head and neck lymphatic malformations. Otolaryngol Head Neck Surg 2007;137:962e4. 22. Nehra D, Jacobson L, Barnes P, et al. Doxycycline sclerotherapy as primary treatment of head and neck lymphatic malformations in children. J Pediatr Surg 2008;43:451e60. 23. Breugem CC, Maas M, Reekers JA, van der Horst CM. Use of magnetic resonance imaging for the evaluation of vascular malformations of the lower extremity. Plast Reconstr Surg 2001;108:870e7.
Background: Because magnetic resonance imaging and angiography are inappropriate for whole-body screening because of high cost or invasiveness, we investigated the potential of whole-body blood pool scintigraphy (WBBPS) as a screening and diagnostic tool for congenital vascular malformations (CVMs). Methods: The subjects of the study were 137 patients (mean age: 20 ± 16 years; range: 0.3e68 years) with suspected CVM. Whole-body anterior and posterior images were acquired twenty minutes after injection of 760 MBq 99mTc-labeled red blood cells (pediatric dose: 13 MBq/kg). The final diagnosis was determined by clinical findings, magnetic resonance imaging, angiography, Doppler sonography, and lymphoscintigraphy. Results: Of these patients, 124 had venous malformations, and 13 had lymphatic malformations. WBBPS successfully detected abnormal blood pooling lesions in 96.8% (120/124) of the patients with venous malformations. None of the patients with lymphatic malformation showed abnormal uptake on WBBPS. In addition, WBBPS detected 41 additional abnormal vascular lesions that were not found during initial clinical evaluation in 16.9% (21/124) of the patients with venous malformations. Conclusion: WBBPS is a valuable diagnostic and screening modality for the initial evaluation of CVM because of its high characterizing accuracy of 97.1% and the ability to image the whole body.
INTRODUCTION Supported by the research fund of Hanyang University (HY-2011-N). 1 Department of Nuclear Medicine, Hanyang University Guri Hospital, Hanyang University School of Medicine, Guri-si, Gyeonggido, Korea. 2
Department of Nuclear Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. 3 Division of Vascular Surgery, Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. 4 Department of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Correspondence to: Joon Young Choi, MD, PhD, Department of Nuclear Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong, Gangnam-gu, Seoul 135-710, Korea; E-mail: [email protected] Ann Vasc Surg 2014; 28: 673–678 http://dx.doi.org/10.1016/j.avsg.2013.02.025 Ó 2014 Published by Elsevier Inc. Manuscript received: October 11, 2012; manuscript accepted: February 12, 2013; published online: December 2, 2013.
Congenital vascular malformation (CVM) is one of the most difficult conditions to diagnose and treat.1 Its clinical presentation is extremely variable, ranging from an asymptomatic birthmark to a lifethreatening condition. This variation is a major challenge for even the most experienced clinicians.2,3 The accurate diagnosis and classification of patients with CVM is therefore important. Based on the predominant component of the vascular defect, CVMs are classified into arterial, venous, lymphatic, arteriovenous shunting, combined (mostly hemolymphatic), or capillary types.4e6 Classification is essential, because the treatment and prognosis of CVMs differ according to type. Even though traditional arteriography and phlebography remain the criterion standards for determining CVM type, they are too invasive to be diagnostic or screening tools for CVM. Therefore, 673
674 Kim et al.
Annals of Vascular Surgery
many noninvasive diagnostic modalities have been developed.3 Of these modalities, magnetic resonance imaging (MRI) and duplex ultrasonography have become the most used, not only for initial diagnosis but also for assessing the results of treatment with multisession therapy.7,8 MRI usually provides conclusive evidence for proper differentiation between venous malformation (VM), lymphatic malformation (LM), and hemangioma, and is excellent for characterizing and discriminating the extent of vascular lesions. It is becoming the criterion standard for CVM diagnosis, replacing the classic role played by angiography.9 Both MRI and duplex ultrasonography have some limitations as techniques for CVM diagnosis and management. Using MRI for whole-body screening for additional lesions and for frequent follow-up assessment is costly,6,10 and duplex ultrasonography is limited in its ability to detect deep lesions and lesions adjacent to air or bone.6,11 An alternative method for the diagnosis and management of CVM is whole-body blood pool scintigraphy (WBBPS) using 99mTc-labeled red blood cells (RBCs). This method is based on the principle of gated blood-pool radionuclide ventriculography. It was first adopted as a supplementary test to reinforce modalities such as ultrasonography, MRI, and angiography, and has been used extensively at our institute for several years.10,12 Currently, WBBPS is used not only as an initial diagnostic test for CVM, but also as a follow-up test, because it has several advantages over the established techniques of CT, MRI, and angiography, including safety, noninvasiveness, and low cost.10,13e15 In addition, it has the potential to detect additional vascular lesions because of its whole body scanning capability. Therefore, in this study, we investigated the role of WBBPS as a diagnostic and whole-body screening tool for CVM.
erythrocyte labeling method. Stannous medronate was injected intravenously; then, after 15 minutes, 5 mL of blood was withdrawn into a syringe containing anticoagulant (ACD-A). The erythrocytes in this sample were labeled with 760 MBq/kg (for adults) or 13 MBq/kg (for children) of 99mTc. The labeling efficiency was >90% in all cases. The radiolabeled erythrocytes were then injected back into the patient. Whole-body imaging was performed 20 min after injection of the radiolabeled erythrocytes.10
METHODS
Of the 137 patients studied, 124 proved to have VMs (87 in the extremities, 25 in the head and neck, and 12 in the trunk). The remaining 13 patients were diagnosed with LMs. WBBPS had a high sensitivity of 96.8% (120/124) for the diagnosis of VMs by the presence of abnormal blood pooling lesions. Figure 1 shows a representative WBBPS result for VMs. The 4 patients with VMs who were found to be negative by WBBPS had very small vascular lesions. However, abnormal blood pool uptake was not observed by WBBPS in any of the 13 patients with LMs, giving a 100% specificity for diagnosis of VMs. Figure 2 shows a representative result of a WBBPS and a lymphoscintigram positive for LM. Therefore, WBBPS had an accuracy of
Subjects The subjects of this study were 137 consecutive patients with suspected CVM. The mean age of the patients was 20 ± 16 years (range: 0.3e68 years). Sixty-three patients were men, and 74 were women. All patients underwent 99mTc-RBC WBBPS at Samsung Medical Center, Seoul, Korea. Whole-Body Blood Pool Scintigraphy A dual-head gamma camera (Biad; Trionix Research Laboratory, Twinsburg, OH) was used for WBBPS. Erythrocytes were labeled by a modified in vivo
Analysis Scintigraphic results were interpreted by the consensus of 2 nuclear medicine physicians. Abnormally asymmetric blood pool lesions were considered to be a blood pooling CVM, such as a VM. If there was no significant abnormal blood pooling lesion, the clinically suspected lesion was considered to be a noneblood pooling CVM, such as an LM or other pathologic lesion. When abnormal focal blood pooling lesions were detected at locations other than the clinically suspected sites, additional diagnostic work-up was recommended. The final diagnosis was determined by clinical assessment of clinical findings, regional MRI (n ¼ 137), angiography (n ¼ 92), and Doppler ultrasonography (n ¼ 94). Twenty-eight patients with suspected LMs on initial study underwent additional radionuclide lymphoscintigraphy. Ethics The institutional review board of Samsung Medical Center approved this retrospective study protocol, and informed consent was waived.
RESULTS
Vol. 28, No. 3, April 2014
Blood pool scintigraphy for evaluating CVM 675
Fig. 1. (A) Whole-body blood pool scintigraphy (WBBPS) and (B) magnetic resonance imaging (MRI) scans of a 10-year-old female with a vascular malformation in the left lower leg. The WBBPS image reveals
abnormal increased blood pooling, indicative of a lesion in the left proximal calf area, and the T2-weighted coronal MRI image reveals a mass with high signal intensity involving the left soleus muscle.
Fig. 2. (A) Whole-body blood pool scintigraphy (WBBPS) and (B) lymphoscintigraphy images of a 45-year-old woman with a lymphatic malformation in the left lower extremity. The WBBPS image shows no significant
abnormal blood pooling, indicating the absence of lesions. In contrast, the lymphoscintigraphy scan shows abnormal accumulation of radioactivity in the left lower leg without visualization of the left main epifascial lymphatic vessels.
97.1% for characterizing CVMs. There was no difference between the 2 interpreters in terms of the presence of abnormal blood pooling lesions. WBBPS detected 41 additional abnormal vascular lesions not found in the initial clinical evaluation, and these were present in 16.9% (21/124) of the patients with a VM (Figs. 3 and 4). Additional assessment techniques, such as MRI or angiography, were performed
on 17 of the 41 abnormal vascular lesions (41.5%), and 14 lesions (82.4%) were proven to be VMs.
DISCUSSION Recently, advances in the diagnosis and management of CVMs have been made because of the establishment of the Hamburg classification (1988),4,16
676 Kim et al.
Fig. 3. (A and B) Whole-body blood pool scintigraphy image of a 22-year-old woman with a congenital vascular malformation in the right cheek area showing abnormal blood pooling indicative of additional clinically unsuspected vascular lesions in the right jugular, right upper back, left lower back, and right calf areas (black arrows).
which provides etiologic, anatomic, and pathophysiologic information on various kinds of CVMs.9 Other advances have been the development of various noninvasive vascular diagnostic tests (e.g.,
Annals of Vascular Surgery
MRI, duplex ultrasonography, WBBPS, transarterial lung perfusion scintigraphy, computed tomography with angiocontrast enhancement, lymphoscintigraphy, ultrasonographic lymphangiography, magnetic resonance lymphangiography, volumetry, and air plethysmography), which are able to provide sufficient information for the accurate diagnosis of various forms of CVMs.7,17,18 MRI in particular is excellent for the accurate characterization of CVMs, especially in the limbs, and the anatomic extent, degree of cellularity, and flow characteristics can be readily gauged. In addition, because it is noninvasive and provides the same basic information as angiography, it can serve as the primary diagnostic test for suspected CVM, particularly in infants and children.8,9 Because of its high cost and limited coverage, it is not suitable for routine whole-body screening. In Korea, regional MRI costs 3 times more than WBBPS. In addition, because MRI is not a whole-body scanning modality, it can only detect lesion in the area on which the MRI is focused, and may not detect any additional sites of CVM throughout the body. In this study, we assessed the use of WBBPS for CVM diagnosis and screening. This technique was previously known as multigated acquisition scanning for cardiac evaluation, but has recently been used in the area of CVM diagnosis and management. In this study, WBBPS was able to diagnose VMs in 120 of a total of 124 patients (sensitivity: 96.8%), showing it to be a highly dependable and sensitive diagnostic method. There were 4 false negative cases in which the lesions were too small to be detected, but this was easily compensated for by other complementary noninvasive tests, such as MRI and duplex ultrasonography. In addition, there was no abnormal blood pooling in any patients with LM. The differential diagnosis between VM and LM is clinically important, because the primary treatment modality is different. For VM, absolute ethanol treatment is used, while sclerotherapy with other agents, such as doxycycline or physical therapy for combined lymphedema, are the main treatment methods for LMs.17,19e22 Although MRI is the most commonly used method of diagnosis for various CVMs, MRI is limited in its ability to differentiate between low-flow type CVMs, such as VMs and LMs.15,23 Considering the high accuracy of WBBPS of 97.1% for characterizing low-flow CVMs, WBBPS may be useful for identifying which treatment is most appropriate for such lesions. This does not mean that MRI should be replaced by WBBPS for evaluating CVM. Regional MRI is still necessary for anatomic information and ruling out other possible diagnoses, such as vascular tumors.
Vol. 28, No. 3, April 2014
Blood pool scintigraphy for evaluating CVM 677
Fig. 4. (A) Whole-body blood pool scintigraphy image of a 2-year-old female with a vascular malformation in the right chest wall revealing abnormal blood pooling indicative of additional clinically unsuspected vascular lesions in the right buttock, back, and left ankle areas (black
arrows). (B) Follow-up T2 fat-suppressed magnetic resonance imaging scan revealing a high signal intensity lobulating mass involving both gluteus medius muscles (white arrows).
Therefore, WBBPS can be an additional diagnostic tool for evaluating CVM. WBBPS detected 41 additional abnormal vascular lesions in 21 patients that were not found in the initial evaluation. Although these lesions were asymptomatic and did not require immediate intervention, the ability to detect additional lesions is important because occult CVMs can grow during follow-up. Early detection allows clinicians to carefully evaluate these lesions during follow-up. Because of the retrospective study design, only 17 lesions could be studied further, and most of these were found to be VMs. WBBPS may provide useful information not only as a screen for previously undetected CVMs, but also as a follow-up test. Previous preliminary studies suggested that, during follow-up, WBBPS yielded not only qualitative image-based measurements of gross changes in the extent of abnormal blood pooling, but also quantitative measurements of the percentage reduction of 99mTc-labeled RBCs in regions of interest, which might permit more precise assessment of the success of treatment.7,19 In this study, because we focused only on the diagnostic and whole-body screening roles of WBBPS, we cannot provide data on the value of follow-up studies. Additional studies to clarify the role of WBBPS in the follow-up of CVM are warranted because of the limitations of previous studies, such as small numbers of subjects.
of its high accuracy, cost-effectiveness, noninvasiveness, and ability to image the whole body.
CONCLUSION WBBPS is a valuable diagnostic and screening modality for the initial evaluation of CVM because
REFERENCES 1. Szilagyi DE, Smith RF, Elliott JP, Hageman JH. Congenital arteriovenous anomalies of the limbs. Arch Surg 1976;111: 423e9. 2. Mulliken JB. Cutaneous vascular anomalies. Semin Vasc Surg 1993;6:204e18. 3. Rutherford RB. Congenital vascular malformations: diagnostic evaluation. Semin Vasc Surg 1993;6:225e32. 4. Belov S. Classification of congenital vascular defects. Int Angiol 1990;9:141e6. 5. Enjolras O. Classification and management of the various superficial vascular anomalies: hemangiomas and vascular malformations. J Dermatol 1997;24:701e10. 6. Kim YH, Choi JY, Kim YW, et al. Characterization of congenital vascular malformation in the extremities using whole body blood pool scintigraphy and lymphscintigraphy. Lymphology 2009;42:77e84. 7. Lee BB, Kim DI, Huh S, et al. New experiences with absolute ethanol sclerotherapy in the management of a complex form of congenital venous malformation. J Vasc Surg 2001;33: 764e72. 8. Pearce WH, Rutherford RB, Whitehill TA, Davis K. Nuclear magnetic resonance imaging: its diagnostic value in patients with congenital vascular malformations of the limbs. J Vasc Surg 1988;8:64e70. 9. Lee BB, Choe YH, Ahn JM, et al. The new role of magnetic resonance imaging in the contemporary diagnosis of venous malformation: can it replace angiography? J Am Coll Surg 2004;198:549e58. 10. Lee BB, Mattassi R, Kim BT, et al. Contemporary diagnosis and management of venous and arterio-venous shunting malformation by whole body blood pool scintigraphy. Int Angiol 2004;23:355e67. 11. Hyodoh H, Hori M, Akiba H, et al. Peripheral vascular malformations: imaging, treatment approaches, and therapeutic issues. Radiographics 2005;25(suppl 1):S159e71.
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