Radionuclide Venography

NMT 431

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What is a Deep Vein Thrombosis

• A) a clot that could infarct the brain• B) a clot that could infarct the heart• C) a clot that could infarct the lungs• D) a clot that could infarct the liver

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A DVT can form because of?

• A) genetics• B) long plane flight• C) spontaneous formation• D) trauma

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Radionuclide Venography is the gold standard for detection of DVT.

• A) True• B) False

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Radionuclide Venography• Imaging of acute deep-vein thrombosis (DVT) in the

lower extremities for patients who do not tolerate radiographic contrast material

• Clinical indications– Equivocal or technically inadequate ultrasound of legs

and high suspicion of acute DVT– Recurrent DVT to differentiate acute from chronic

disease– Acute onset of symptoms– Detection of acute thrombophlebitis (tagged RBC’s)

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Major Veins of the Right Lower Limb

From McClintic RJ. Human Anatomy; 1983.6

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8http://images.lifescript.com/images/ebsco/images/si55551528_ma.jpg

Main Veins of the Leg

DVT Diagnostic Approach

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CLINICAL FINDINGS• LEG PAIN/SWELLING• POSITIVE “HOMAN’S SIGN” (PAIN ON

DORSIFEXION OF FOOT)• PALPABLE “CORD” SUPERFICIAL

THROMBOPHLEBITIS• 1/3 OF DVT’S ASYMPTOMATIC• OF DVT’S FOUND AT AUTOPSY ABOVE CALF,

ONLY 19% HAD SYMPTOMS/SIGNS

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CLINICAL CONT’D.

• CONVERSELY, VENOGRAMS (+) FOR DVT IN ONLY 46% OF CLINICALLY SUSPECTED CASES

• DDX:– CELLULITIS– BAKER CYST (ESPECIALLY WITH RUPTURE)– HEMATOMA– ETC.

• CLINICAL FINDINGS: UNRELIABLE

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http://www.consumerreports.org/health/resources/images/conditions/dvt-rash_default.jpg

http://img.medscape.com/pi/emed/ckb/vascular_surgery/459840-462390-3304.jpg

http://www.my-varicose-veins.com/images/phlebitispic.jpgPhlebitis

DIAGNOSTIC METHODS• CLINICAL (observation)

• CONTRAST VENOGRAM– SPIRAL CT

• DOPPLER(ultrasound)• D-DIMER (blood test)• NUCLEAR

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Gold Standard

http://golds-coins.com/wp-content/uploads/2011/07/Gold-Coins-Pictures.jpg

Contrast Venography– “Gold Standard” for imaging DVT - when technically

adequate– can image entire lower extremities– sensitive in asymptomatic patients

Limitations – painful– technically inadequate/difficult to interpret in 10-30% of

cases1,2

1. Hirsh J et al. Circulation 1996; 93:2212-2245. 2. Anand SS et al. JAMA 1998; 279:1094-1099.

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DVT

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DVT

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DVT

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CONTRAST VENOGRAPHY CONT’D.COMPLICATIONS OF CONTRAST

VENOGRAM

• DVT CAUSED BY DYE IN PT WITHOUT DVT– IONIC CONTRAST - UP TO 25%– NONIONIC CONTRAST - UP TO 7%– NON ISOSMOLAR, NONIONIC - STUDIES

PENDING• ALLERGIC REACTION• RENAL AND OTHER TOXICITIES• DEATH

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DIAGNOSTIC METHODS

• CLINICAL• CONTRAST VENOGRAM

• DOPPLER• D-DIMER• NUCLEAR

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DUPLEX DOPPLER ULTRASOUND

• ONLY RELIABLE FROM INGUINAL LIGAMENT TO TAKE-OFF OF TIBIAL VEINS

• MULTIPLE TRIALS:– 92% SENSITIVITY (FOR ALL CLOT IN

LEG, EVEN THOUGH CALF VESSELS NOT SEEN)

– 99% SPECIFIC

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DOPPLER CONT’D. METHOD

• PULSED DOPPLER/BETTER WITH COLOR

• COMPRESSION AT EVERY LEVEL FROM UPPER COMMON FEMORAL TO LOWER POPLITEAL (EVEN IF CLOT NOT SEEN, INCOMPLETE COMPRESSABILITY SUGGESTS PRESENCE OF CLOT)

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NORMAL WITHOUT COMPRESSION

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NORMAL WITH COMPRESSION

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PARTIALLY OBSTRUCTING THROMBUS

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Ultrasonography

Advantages

– high sensitivity (82-100%) for proximal DVT (thighs and knees) in patients with localizing signs and symptoms1

– fast– low cost per procedure

1. Rose SC. RSNA Categorical Course in Vascular Imaging. 1998:139-156.

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DRAWBACKS TO VENOUS DOPPLER

• HEAVILY OPERATOR-DEPENDENT• SOME SEGMENTS MAY BE “BLIND” TO

SAMPLING• CALF VEINS USUALLY NOT STUDIED, BUT

WITH NEW GENERATION EQUIPMENT CALF VEINS CAN BE RELIABLY SEEN IN 60-90%; IF SEEN, DOPPLER 90% SENSITIVE AND SPECIFIC FOR CLOT IN THEM.

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Anatomic Imaging Modalities

• Contrast Venography and Ultrasonography•

– not specific for acute DVT– cannot reliably differentiate acute from

non-acute DVT

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DIAGNOSTIC METHODS

• CLINICAL• CONTRAST VENOGRAM• DOPPLER

• D-DIMER• NUCLEAR

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D-DIMER: BLOOD TESTING FOR ACUTE THROMBOSIS

• DEGRADATION PRODUCT OF CIRCULATING CROSS-LINKED FIBRIN

• ELEVATED LEVELS IN ACUTE THROMBOSIS

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RECENT LITERATURE REVIEW: (BECKER, et al ARCHIVES INT MED, MAY ‘96

• VARIOUS ASSAYS NOT STANDARDIZED (ELISA, LATEX, IMMUNOFILTRATION)

• STUDIES HAVE NOT LOOKED FOR PRESENCE OR ABSENCE OF BOTH DVT AND P.E.

(I.E. PT’S CONSIDERED FREE OF P.E. MAY HAVE HAD SILENT DVT, AND VICE VERSA)

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DIAGNOSTIC METHODS

• CLINICAL• VENOGRAPHY• DOPPLER• D-DIMER

• NUCLEAR MEDICINE

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NM Clinical Procedure

1) ID patient; verify physician’s order; review clinical indication for exam

2) Explain procedure to patient; obtain relevant medical history

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Relevant Medical History

• Location/duration of edema, warmth, redness, pain in lower extremities

• Prior history of DVT• Arthritis/cellulitis• Varicose veins• Results of US • Results of d-dimer

test

• Predisposing factors– Recent pelvic, hip,

knee surgery– Recent trauma– Cancer– Estrogen therapy– Recent travel– CHF– Obesity– Family hx of

thrombosis

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Clinical Procedure - cont’d3) Administer radiopharmaceutical intravenously

a) Tc-99m apcitide (Acutect) ~20 mCi( Note: This agent is not commercially available at this time)

A synthetic peptide that binds to activated platelet receptors, part of the blood clotting process. Because the peptide binds to activated receptors, it identifies acute (clots in the process of forming) from chronic thrombosis

b) 99m-Tc Maa ~6 mCi

c) 99m-Tc tagged RBC’s ~20-30 mCi

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Clinical Procedure - cont’d4) Image patient (for Acutect)

Anterior/posterior: pelvis, thighs, knees, calves at 10 min and 60-90 min post injection

5) Sources of error ( for Acutect)- excess bladder activity- urinary catheter tubing/urine contamination- increased uptake in postsurgical sites, collateral or superficial veins

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NUCLEAR VENOGRAPHY• 99MTc-MAA – injection in each foot dorsal

vein• SENSITIVITY 94%/SPECIFICITY 92%

(SIEGEL, USC)

• PRO’S: – LUNG PERFUSION; ILIACS/IVC

• CON’S: – CALF VEINS; NONOBSTRUCTING CLOT

WITHOUT COLLATERALS

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Typical Positive DVT Nuclear Scan

Anterior Posterior

http://www.agenix.com/agen/images/picTV_info02.jpg

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99m-Tc tagged RBC’s

• IV injection of tagged cells

• Normal: veins appear and disspate with time

• Abnormal: higher uptake in tissue and areas of swelling

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Tc-99m Apcitide Scintigraphy• Specific for Acute DVT

NO Longer Commercially Available

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Tc-99m Apcitide

GPIIb/IIIa binding region

99mTcapcitide

– a small synthetic peptide– 13 amino acids, mol. wt. 1392 Da

– binding region for the platelet GPIIb/IIIa receptor

– radiolabeled with Tc-99m 45

Binding to Platelet GPIIb/IIIa Receptors

fibrinogen

PlateletPlatelet

99mTcTc-99m apcitide

GPIIb/IIIa

GPIIb/IIIa Activated PlateletActivated Platelet

Tc-99m apcitideand fibrinogenbind to theGPIIb/IIIa receptors onactivated platelets

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Tc-99m Apcitide

• How It Worked– Activated platelets are present in acute

thrombi– The GPIIb/IIIa receptor is expressed on

activated platelets– Tc-99m apcitide binds to the GPIIb/IIIa

receptor– Unbound Tc-99m apcitide clears rapidly

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Advances in the Diagnosis ofVenous Thromboembolism

– Venous Thromboembolism• Clinical Importance • Diagnosis and Treatment

– Tc-99m Apcitide• Mechanism of Action• Clinical Results

– Clinical Applications

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Imaging Acute DVT with Tc-99m Apcitide

• Standard Procedure– 20 mCi Tc-99m, 100 g peptide– Antecubital vein injection– Standard nuclear medicine gamma camera– Anterior and posterior planar images starting at 10 min

and 60-90 min

In some cases:– SPECT or delayed (3 h) planar images useful

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Tc-99m Apcitide Normal Biodistribution

10 min 60 min 240 min

R anterior L L posterior R R anterior L L posterior R R anterior L L posterior R

41 year old female50An “Aunt Minnie” Type Scan www.auntminnie.com

Tc-99m Apcitide Negative Case 10 min 60 min 120 min

R anterior L L posterior R

R anterior L L posterior R

R anterior L L posterior R

Patient History: 34y female, no prior history of DVT or PE, 2 days from onset of signs and symptoms in right calf, knee and thigh; venogram negativeTc-99m Apcitide Findings: negative for acute DVT

239551

Tc-99m Apcitide Positive Case

10 min 60 min 120 min

R anterior L L posterior R

R anterior L L posterior R

R anterior L L posterior R

Patient History: 66y male, prior history of DVT and PE, 5 days from onset of signs and symptoms in right calf and knee, on heparin and warfarin; venogram positive right calf and popliteal veinsTc-99m Apcitide Findings: acute DVT in right calf, knee and (distal) thigh 437052

Tc-99m Apcitide

•Biodistribution and Dosimetry– rapid urinary excretion over 24 hours (84-99%)– hepatobiliary excretion = 6% over 24 h– blood pool approx. 10% ID at 60 min– mean effective dose equivalent = 0.034 rem/mCi– maximum absorbed radiation dose (to urinary

bladder wall) = 0.22 rad/mCi– estimated biological half-life = 1.9 h

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References

• Pete Shackett, 2nd edition, Nuclear Medicine Technology Procedures and Quick References

• http://www.nucmedtutorials.com/pp/dvt.ppt

• http://www.clevelandclinicmeded.com/medicalpubs/micu/diagnosticdvt.htm

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