Hepatobiliary Imaging - A & P - Radiopharmaceuticals - Diseases

1. Purpose of this exam is to examine and evaluate hepatobiliary flow in the liver
1. Hepatocytes pick up the radiopharmaceutical
2. Bile flows through the hepatic ducts
3. To the cystic duct and gall bladder
4. Bile flows out of the gall bladder into the common bile duct, then into the duodenum



Right Hepatic Duct (RHD) Left Hepatic Duct (LHD) Common Hepatic Duct (CHD) Cystic Duct (CD) Gallbladder (GB) Common Bile Duct (CBD) Sphincter of Oddi (SOO) Duodenum (D) Falciform Ligament (FL)

2. Diagram of the hepatobiliary tree

3. Normal hepatic flow
4. Hepatobiliary Agents - these types of radiopharmaceuticals will be identified as ^99mTcIDA or IDA. By forming different N substitutions on the carbon ring, different forms of IDA (Iminodiacetic acid) have been produced:



1. ^99mTc HIDA (dimethyl)
1. The original agent
2. In a normal functioning liver 85% of this agent is excreted via liver and 15% is excreted by the kidneys
3. Increased levels of bilirubin reduce hepatic uptake with increased kidney uptake
4. Acceptable bilirubin level for hepatobiliary imaging is up to 5 - 7 mg/dL



2. ^99mTc DISIDA (Disofenin) (Hepatolite)
1. Normal functioning liver: 88% of this agent is excreted by the hepatic system with 10% by the kidneys
2. Acceptable visualization of the hepatobiliary tree can occur with up to 20 mg/dL of bilirubin



3. ^99mTc BROMIDA (Mebrofenin) (Choletec)
1. Has the greatest hepatic uptake at up to 98%
2. Least affected by high levels of bilirubin
4. General comments on IDA physiology
1. Once injected, IDA binds to plasma protein, which reduces renal excretion
2. IDA competes with bilirubin at the same sites of extraction on the hepatocytes, via a process known as competitive inhibition
3. The greater the level the level bilirubin, the less the uptake of IDA and the greater the renal excretion
4. IDA and bilirubin are extracted by the hepatocyte via active transport
5. Improved IDA extraction occurs when the compound is more lipophilic, creating a stronger protein bond. Reduces renal extraction
6. Increasing the length of the alkyl chain substituted on the benzene (carbon) ring also improves biliary excretion and reduces renal excretions
7. Therefore, DISIDA and BROMIDA are the preferred radiopharmaceuticals when patient have high levels of bilirubin


5. How is bilirubin/bile produced? (Refer to diagram)


1. Heme is the source of bile pigment
2. Heme is the end product in hemoglobin breakdown that results in 80 to 90% of the bilirubin produced in adults
3. As stated above, bilirubin and IDA competes for the same sites on the hepatocytes
4. Hepatocytes are also referred to as parenchymal cells
5. More on bile production
   1. Hepatocytes produce between 500 and 1000 ml of bile per day.
   2. From the hepatocytes bile is secreted into tiny bile calculi that run between hepatocytes and drains into branches of the bile ducts located in the portal triad
   3. Eventually this merges with the right and left hepatic ducts, which both connect to the common hepatic duct
   4. The common bile duct is starts where the common hepatic duct meets the cystic duct meet
   5. The cystic duct connects to the gal bladder that is about 10 cm in size and stores around 50 mL of bile. When fatty chyme reaches the enteroendocrine cells within the duodenum this stimulates the vagus nerve that causes CCK production. CCK then stimulates the gal bladder contraction and relaxation of the sphincter of Oddi. Bile then flow down the common bile duct into the duodenum

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6. A look at GB diseases
1. Gee, let's first make a comment or two regarding a normal scan
1. Normal bile flow throughout the hepatic system
2. Gall bladder images within the hour
3. EF of the GB is >38%
2. Acute cholecystitis
1. Gall stone blocking the cystic duct
2. Gall bladder does not image
3. Chronic cholecystitis
1. Temporary blockage of the cystic duct
2. Gall bladder appears post 1-hour injection
4. Acalculous cholecystitis (vs. calculous)
1. Blockage without stones
2. Slug/inflammation of the gall bladder
3. If or when the gallbladder fills, there is a reduced injection fraction when sincalide is administered (synthetic form of CCK)
5. Other Blockages within the hepatic tree
1. Calculous or tumor
2. Activity maybe blocked at the R or LHD, CHD, CBD, or small intestine
6. Bile leak
1. Usually follows postoperative removal of the gall bladder
2. Activity empties into the surrounding gallbladder fossa and/or the hepatic tree
7. Bile reflux
1. Bile refluxes upward from the duodenum
2. Activity is noted at or above the left lobe of the liver
8. Gallbladder perforation
1. High mortality occurs when surgical intervention is not completed
2. Does not have to occur with cystic duct obstruction
3. More common in elderly patients and/or chronic cholecystitis
9. Biliary atresia vs. neonatal hepatitis
1. Performed on new born infants
2. The question, "Is the hepatobiliary tree connected to the small intestine in the jaundice infant?"
3. (From a historical perspective) I-131 Rose Bengal was used prior to the development of IDA
1. Dose was administered
2. Followed by a 72 hour fecal collection
3. Fecal material was mixed into a single container to determine the amount of mL
4. A sample of the fecal material was counted, multiplied by the total mL, and the excreted dose was compared to the dose administered
5. If less than 5% percent of the dose was excreted, biliary atresia was diagnosed
4. (Today's current approach) Prior to the IDA scan, the infant is dosed with 2.5 mg/kg orally BID for 5 to 7 days with phenobarbital
1. Phenobarbital improves excretion of IDA through the hepatobiliary tree
2. If activity is not seen in the small bowel, then biliary atresia is diagnosed

1. Normal hepatobiliary image
1. Early images show vascular activity, mostly above the dome of the liver (myocardium)
2. Hepatic cells quickly extract the IDA from the vascular pool identifying the entire liver (hepatocyte extraction of IDA)
3. Hepatic ducts and common bile ducts visualize within 30 minutes and activity dumps into the duodenum
4. Within 60 minutes the gallbladder should appear
5. Non-vis of the GB maybe due to patient fasting (more than 24 hours). Administration of a fatty meal or CCK prior to the study is suggested
6. Pending the level of bilirubin activity, kidneys and urinary bladder may also be visualized
7. Any deviation from the above usually indicates some type of dis
   ease
8. Perfusion defects in the liver may also be noted which could indicate hepatocellular disease or space occupying lesion(s)


2. Protocol - General
   1. Patient preparation
      1. NPO for at least 2 hours
      2. Morphine Sulfate (MS) oral - d/c for 2 - 4 hours
      3. MS IV d/c 2.1 - 2.6 hours
      4. Diaudid/hydromorphone - d/c at least 8 hours
      5. Fentanyl patch d/c at least 8 hours
   2. Collimation LEHR
   3. Dynamic - matrix size 128 x 128
   4. Static - matrix 256 x 256
   5. Zoom if pediatric
   6. Adult dose 6 mCi
   7. Pediatric dose 0.05 mCi/kg
   8. Image supine - make the patient comfortable since imaging may take at least 1-hour
   9. Dynamic Imaging
   10. If the GB and small intestines visualize the procedure is complete, unless an EF of the GB is required (see below)
   11. If the GB does not visualize
       1. Continue imaging and/or administer morphine sulfate (MS) [see below]
       2. If MS is not administered imaging should continue, however, imaging time may vary pending department protocol
3. Dynamic Imaging - 1-minute images for 60 minutes
4. Static Protocol - suggest images every 5 minutes for 60 minutes at 500k ti 700k counts
5. Regarding non-vis of the GB and acute cholecystitis
1. Detection - sensitivity 95% and specificity 99%
2. Symptoms for acute cholecystitis: URQ pain, nausea, vomiting, fever, and/or elevated white blood count (and sometimes elevated bilirubin level)

 


1. Types of calculi
2. Usually caused by calculi blocking the cystic duct
3. 5 to 15% have acalculous
4. Rim sing
1. Activity is seen in and around the gallbladder fossa as a "rim" of activity
2. Results from tracer retention and bile status in an inflamed, edematous gallbladder where activity does not enter the GB
5. False positive results can be caused by
1. If the patient has not been fasting for less than two hours GB which may cause delayed or no visualization of the GB
2. Patients on total parenteral nutrition (TPN)
3. Prolong fasting (24 hours or more)
4. Chronic cholecystitis is the cause
5. "Sludge" accumulation in the GB remedied by the administration of CCK 20 to 30 minutes prior to IDA injection
6. CBD obstruction
7. Hepatocellular dysfunction (due to poor tracer uptake and slow blood clearance of IDA


6. Morphine sulfate augmentation
1. Administered when there is dumping of the tracer into the small bowel, but no activity is seen in the GB
2. Without morphine delay, images should be done for at least 4 hours
3. If activity is not seen in the GB after 1 hour, administer 0.04 mg/kg morphine IV for 2 to 3 minutes
4. Assume you have a 214 lb patient, what amount of MS would you administer? Ans
5. Causes constriction of the Sphincter of Oddi with pressure building up in the CBD
6. Continue imaging every 5 minutes for up to 30 minutes
7. If GB does not visualize, then acute cholecystitis is diagnosed
8. CCK should not be administered with this procedure
9. If CCK is used pre- or post-morphine, a 30 minute delay for administering the second pharmaceutical must be followed (Issue? The T_1/2 of MS is 2 hours)


7. CCK augmentation (Kinevac or Sincalide)
1. Kinevac (CCK derivative)
1. See package insert - How is this agent reconstituted?
2. Should be given to the patient if he/she has been NPO for greater than 24 to 48 hours
3. Reason - GB stasis
4. Kinevac dose = 0.02 μg/kg of body weight
5. Dose patient 30 minutes prior to IDA injection
6. Causes contractility of GB reducing a false positive study
2. Determination of GB ejection fraction (see formula below)

1. Determine when the GB is at maximum filling
2. Inject Kinevac IV over a 3 minute period of time or (administer as IV drip 30 to 45 minutes - see discussion)

3. Kinevac dose = 0.02 μg/gm of body weight
4. Post 5 minutes take an image for every 5 minutes for a total of 20 minutes
5. Draw an ROI over the PreCCK of the GB - Should you preset the time after this or just go for a specific amount of counts?
6. Draw an ROI over every other GB image that is acquired
7. Plug in the numbers to the above formula to determine %EF of the GB
8. If the EF of the GB is <30% chronic cholecystitis is diagnosed
9. If the EF is between 30 and 35%, it is indeterminate
10. If the EF is >35% the GB is considered normal
11. Note: It is very important to administer exactly over a 3-minute period using a pump. Manual administration may alter the %EF of the GB
3. Substituting Sincalide
   1. When not available and lactose-free fatty meal is given PO
   2. Dose - 240 mL containing 11.4 gm of fat - Ensure Plus
   3. Krishnamurthy and colleagues dosed 13 health volunteers with CCK-8 IV (3 ng/kg/minute for 10 minutes). This was followed up with an half-and-half at a later time
      1. Ensure Plus mean was 53.6% ± 20.2%
      2. CCK-8 (sincalide) EF first dose mean was 75.8% ± 16.3%
      3. CCK-8 EF second dose mean was 71.3% ± 17.4%
   4. Data should be acquired for 60 minutes
   5. Lower end of normal EF for sincalide substitute is 33%
8. Comments regarding the EF of the GB
1. Pomeranz, et al studied 30 normal volunteers and 67 patients with chronic disease

1. 20ng/kg of sincalide was administered over a 15-minute period
2. Mean %EF for the normal group was 74.8 (SD 19.8%)
3. Mean %EF for the abnormal group was 56.4 (SD 27.5%)
4. Two negative SD in the normal group falls at to 35.2%
5. Two positive SD in the abnormal group is greater than 100%
6. Do you have a problem with these numbers?
7. Where does the abnormal deviation lie when compared to normal?
2. Ziessman, et al compared the 3-minute administration of CCK with a 30-minute infusion using a 0.02 μg/kg dose on 23 healthy volunteers
1. Using a cutoff of >35% EF for normal
1. 74% of the patients had a normal EF using the 3-minute administration
2. 91% with the patients had a normal EF using the 30-minute infusion
2. In addition, patients receiving the 30-minute infusion had no CCK-side effects while the 3-minute injection of CCK did
3. Sarva, et al administered 20 ng/kg of octapeptide-CCK to 22 normal volunteers and varied the time of administration
1. Mean %EF at 45 minutes infusion rate was 77.2% (SD 4.9%)
2. Mean %EF with a rapid 1-minute injection was 52.2 (SD 9.3%)
3. Hence, variation of the administered dose over time does affect the %EF of the GB
4. Also, no side effects were noted with patients receiving the 45-minute infusion
4. Read the following discussion on the applications of Kinevac
3
5. Finally an article came out by Dr. Ziessman that assessed all the issues that revolved around EF of the GB. Above is a chart that shows you the variations of different investigators with different infusion rates and variation of EFs. The multi-trail assessment concluded:
   1. 0.02μCi/kg administered over 60 minutes
   2. The value to calculate the EF of the GB should be done at the 60 minutes image
   3. This method had the lowest coefficient of variation
   4. The lowest range of number was 38%


9. Comments on Imaging
1. Questionable GB uptake around the gallbladder fossa
1
1. Take RAO, LAO, and/or R-LAT images


https://www.appliedradiology.org/userfiles/2/files/AR_09-16_TulchinskyCME.pdf

2. Perhaps the best view is the R-LAT to determine if possible uptake is the gallbladder or bowel loop mimicking the GB uptake on the ANT image
2. Non-vis of the GB with extensive activity in the small bowel
1. If the majority of counts in coming from the small intestine, minimal activity in the GB maybe missed
2. Shield the small bowel to increase the count density in the area of interest (GB)
3. This becomes crucial in delayed imaging
3. If the EF of the GB is < 35% administer a second dose of CCK
1. Sludge in the GB maybe forced out in the first dose of CCK
2. Second dose may than improve %EF
4. Possible CBD obstruction - How long do you image?
1. Imaging should be done up to 24 hours post dose of IDA
2. Delayed images may show some activity passing through the CDB indicating only particle CBD obstruction
5. Never inject CCK and morphine within 30 minutes of one another


10. Questions
1. What causes increased levels of bilirubin?
2. How would increase levels of bilirubin effect imaging quality using IDA?
3. What is the difference between neonatal hepatitis and biliary atresia?
4. When is CCK used in hepatobiliary imaging?
5. When is morphine used in hepatobiliary imaging?
6. Identify the flow of bile, from the hepatocytes to the small bowel.

Case 1 The first case you've seen before. It is an animated .gif showing bile moving through the hepatobiliary system. In these images you should be able to identify the GB and small intestine, all of which imaged within 60 minutes after the patient was injected (this is considered normal). However, there is an abnormal accumulation of activity seen just below the left lobe of the liver. This abnormal accumulation of activity is known as bile reflux.

This case is an example of a normal hepatobiliary scan. The 5-minute image shows normal perfusion of the radiopharmaceutical in the hepatic cells. The 5-minute image shows activity in the myocardium, which is seen above the left lobe of the liver. The 15-minute image identifies activity flowing all the way to the small intestine. At 50-minutes the gall bladder contains radio-bile, indicating that the cystic duct is patent.

The third case is an example of a patient with a high bilirubin level and partial common bile duct obstruction. All images show poor perfusion of the radiopharmaceutical in the liver. The gallbladder images at 75 minutes, with no activity in the small intestine. In addition, the right lateral view at 80 minutes shows a very hot kidney, indicating that a lot of the radiopharmaceutical being excreted by the kidneys (indicating a high bilirubin level). From a technical standpoint, the gallbladder is shielded at the 2-hour image to increase the count density around the surrounding tissue. This results in picking up a small amount of activity being excreted into the small intestine. Finally, the 7-hour image, shows activity in the small bowel. Because of the length of time taken for radio-bile to reach the small intestine, partial small bowel obstruction is indicated. Partial obstruction may be do to tumor or a gall stone.

The following parts are labeled in the images below: a) gall bladder; b) activity in the femoral arteries; c) right lobe of liver; d) kidney; e) shield over gall bladder; f) activity in blood pool (myocardium); and g) small intestine.

The following parts are labeled in the sonogram image taken in B Mode - left: a) shadowing caused by stones; b) gall stones; and c) gall bladder wall. On the right is an image which displays 3D image of a large gall stone.

Case 5

Regarding this hepatobiliary scan, the selected images show: normal liver perfusion of the radiopharmaceutical; activity dumping into the small bowel at 30 minutes post injection. At 2-hour there is no activity seen in the gall bladder. This is an example of acute cholecystitis.

Question: From a technical standpoint, how might you further confirm that there is no gall bladder activity in the 2-hour image?

This is an example of a bile leak, which occurred after surgery, caused when this patient underwent laparoscopic cholecystectomy. Two weeks after surgery the patient was examined in the ER and complained of vomiting, low grade fever, and tenderness in the URQ of the abdomen

The hepatobiliary images indicate a bile leak. CT further confirms that presences of a leak. A French Elecath was implanted and drained the site for four days. A second set of CT images indicate that the leak has been repaired and the fluid has been drained.

http://www.med.harvard.edu/JPNM/TF94_95/Feb7/WriteUpFeb7.html

Patient has URQ pain. No bile flow is seen on the two or twenty-four hour images. What what do you think is going on? Answer

http://www.filmjacket.com/readarticle.php?article_id=17

Following the delayed images of a hepatobiliary scan activity is noted distal to the left lobe of the liver (arrows). Why are the arrows pointing at and how can you explain this abnormal accumulation of activity? Answer

http://jnm.snmjournals.org/cgi/content-nw/full/45/6/1004/F2

Case 9

Patient underwent laparoscopic cholecystectomy five days prior to this study. She was admitted to the ER with belly pain and vomiting. The above hepatobiliary was taken over 60 minutes. What is your impression? Answer

http://www.nuclearonline.org/Newsletter/CaseStudy604.htm

Here is a case in which a patient was first given CCK half-an-hour prior to injecting the IDA agent. Sixty minutes later MS was administered. What is your diagnosis?

Case 11

&

Patient is s/p open cholecystectomy, presented to the emergency room on post op day 10 with abdominal pain and vomiting. Answer

Case 12

After 1 hour of imaging the following image is taken. The arrows in the image is an indication of what? Roll your mouse over the image and you will see an ultrasound of the gal bladder. Answer

http://rad.usuhs.edu/medpix/parent.php3?mode=pt_printer&pt_id=7617&showall=yes

Case 13

Following the administration of Bromida the above images where taken. 1) Would you inject CCK-8 to determine EF of the GB? 2) What appears to be going on with this patient? Answer

Case 14

There are two scans of two different infants that underwent a hepatobiliary scan for the assessment of biliary atresia/neonatal hepatitis. 1) Define the corresponding disease. 2) Identify the preparation required before the hepatobiliary scan is administered.

This is an example of the dynamic acquisition to assess gal bladder ejection fraction. Kinevac is administered for 1 hour. ROIs are drawn over the GB and a time activity curve is generated. Based on the information generated does the patient have acalculous cholecystitis?

For a review of this material you may also look at a Hepatobiliary Imaging presentation that is also available through SNMMI

Please not that most of the links that document the images in this presentation are no longer active.

Hepatobiliary Procedure
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11/22

References

1. Nuclear Medicine Technology Resources - http://www.nucmedreview.com/cases/gi/gi.html
2. Ultrasound Images - http://www.ultrasound-images.com/gall-bladder.htm
3. Sincalide-Stimulated Cholescintigraphy: A Multicenter Investigation to Determine Optimal Infusion Methodology and Gallbladder Ejection Fraction Normal Values by Ziessman, et. al.