Yttrium-90 Bremsstrahlung Imaging

Yttrium-90 imaging is probably not the first thing that comes to mind when scanning in Nuclear Medicine as an isotope, namely because it is outside of the realm of our usual Technetium-99m based radiopharmaceuticals. I have written about Y-90 and Theraspheres in the past blogs (parts I and II), but this time instead of discussing the treatment aspect, we will look at the imaging aspect of using Y-90 and its Bremmsstrahlung x-rays that it produces.

Imaging was performed on a patient who was diagnosed with hepatocellular carcinoma.  Early in the treatment planning with computed tomography (CT) and interventional arteriography, a large mass was localized in segment 4A/B in the liver.   Majority of the vascularity was provided by the left hepatic artery.  The middle hepatic artery and gastroduodenal arteries were then coiled embolized to limit perfusion.  This patient was on the third treatment cycle of Y-90 Therasphere.  The growth of the liver lesion was stabilized with the first two treatments but there were some suspicions of new metastases.

Fig. 1  Finding the common hepatic artery during the arteriogram.  Quite honestly, I can not figure how the interventional radiologists navigate through the arteries like that... There are no google maps for this!

Fig. 2  The right hepatic artery.  Notice the blush within the lesion as the contrast was infused.  I find this quite amazing to see in person.  In the end the interventional radiologists decide to use the left hepatic artery to infuse the Tc-99m MAA to determine the lung shunt fraction and in turn was used to infuse the Y-90. 

What we wanted to accomplish was to ensure that the Y-90 Theraspheres that we were infusing had truly localized within the liver segments that we wanted to treat.  In the past we had indirectly measured the activity using a dose rate meter (Bicron - mSv/hr) to examine the exposure rates to various parts of the chest and abdomen after the infusion.  The tricky part of the whole thing was that we had never scanned Bremmsstrahlung x-rays before.

Luckily there is an array of information on the internet, but the problem is trying to decipher all this information.  The Y-90 Bremsstrahlung spectrum looks very different, when low energy all purpose (LEAP), medium energy (ME) and high energy (HE) collimators are fitted onto the gamma camera.

Fig. 3  Top:  Represents the Bremsstrahlung spectra on a gamma camera without collimation.  Second:  Represents the spectra with a low energy all purpose (LEAP) collimator.  Third:  The spectra with a medium energy (ME) collimator.  Bottom:  The spectra with a high energy (HE) collimator.  Note 1:  If anyone who is reading this - can someone confirm what the lower peak is?  (It's a scatter peak of some sort - it may be a dumb question, but I need to ask it for my knowledge).  Note 2:  Diagram was taken from:  Planar Gamma Camera Imaging and Quantitation of Yttrium-90 Bremsstrahlung

Fig. 4  There is a characteristic x-ray photopeak between 75 - 79 keV with collimation.  This is the range where we decide to use our window for imaging.  However, note on the far right in Fig. 3 TOP, and in Fig. 4 another interesting peak occurs on around 180 - 210 keV.  This is probably the result of septal penetration due to some high energy Bremsstrahlung x-rays.

Furthermore, where do we centre the energy window and how big should the window be?  There is a characteristic x-ray peak, as indicated above, around 75 keV.  But what is interesting is that some protocols use a 79 keV peak with a 26% window, while others use a 90 keV peak and a window width of 15%. So what is the optimal imaging parameter in regards to the energy peak and energy window?  I am not really sure, and I think it really has to do with the testing that we need to do on our camera system (Seimens Symbia T-6) to figure this out in terms of sensitivity, resolution and target to background ratios.  However we did not have the luxury of time to test these parameters.  When we first started the trial, it was never our intention to image the Y-90 Therasphere patients, and this patient was a "one off".

However there is some agreement with respect to the collimation.  From what I have read between ME and HE collimators, generally speaking, most have used the ME's.  In our case, the administered dose was approximately 2.03 GBq and imaging was performed 3 days later, we opted for the ME's since there were not going to be any significant differences between sensitivity and resolution between ME and HE collimators for equivalent energy windows (ie. whether we were using a 26% or 15% window).  

So these are our results:

Fig. 5 Coronal fused section from the SPECT/CT (Symbia T-6) with localization in the segment 4 of the liver

Fig. 6  Sagittal fused section from the SPECT/CT (Symbia T-6)

Fig. 7  Transaxial fused section from the SPECT/CT (Symbia T-6)

The MIP after reconstruction looks like a "big blob".  It didn't look too bad with regards to the planar images which we also obtained.  We had captured them to quickly examine the target lesion to background liver fraction.

Fig. 8  Anterior image.  We imaged for 600 secs and obtained approximately 700K to 1700K total counts (posterior/anterior images respectively)

Fig. 9  A quick target lesion to liver background ratio was calculated to determine the amount that remained in the liver 3 days after the infusion

In the end we decided to use the MD Anderson's protocol.  It was a shot:

NM Planar & SPECT Y-90 Bremsstrahlung Imaging:

– 79keV/26% window, MELP collimation, 128x128 matrix, 4.8 mm2 pixels, 128 

views/360°, 28 s/view, non-circular step-shoot

So we did all this, BUT some might say... what about imaging the patient on the PET/CT unit? Well I wish we could, as you know, Y-90 is a beta emitter and this is certainly within the realm of possibilities, and with it, a huge array of literature on this as well.  We thought about it, but we couldn't get imaging time on the PET/CT unit... so we opted for regular gamma camera imaging.  QED.

Normal Uptake on WBI

Fig. 1  Whole body iodine, 10 days post administration of a therapeutic dose of I-131.

Whole body iodine (WBI) imaging was performed on a patient who was administered 3.7GBq of I-131 ten days prior for papillary carcinoma.  A total thyroidectomy was also performed as part of the treatment process earlier in the year.

For the most part the thyroid bed was unremarkable as well as the rest of the image, except for a focal uptake in the right upper quadrant.  Generally the technologists are fairly cautious at our facility, since a metastatic survey was being performed, a SPECT/CT of the area was also included in the study.

Fig. 2 Coronal section of the SPECT/CT, noting the uptake within the liver.  Most likely being gallbladder uptake of the I-131.

Fig. 3  Transaxial CT used in conjuction with the SPECT to localise the I-131 uptake.

Fig. 4  Fused transaxial SPECT/CT, confirming the uptake of the radioactive iodine is inside  the gallbladder.

Why is this interesting?  Well for one thing, this is something that we do not normally see on our WBI images.  Normally we see diffuse liver uptake in this area,  but it is not totally uncommon to visualise the gallbladder.  This is well documented in the literature and the article does discuss some possibilities of what can potentially cause this normal uptake.  Conditions such as cholecystitis, hypokinetic gallbladder function due to stones or an abnormal gallbladder morphology are just some of the potential reasons.  Most often an ultrasound is ordered to confirm or correlate if there are any underlying issues that may be involved with the gallbladder.

Bottomline, gallbladder uptake is normal.  It is not commonly seen, but from a technical perspective we would rather be "safe than sorry" by performing extra imaging such as a SPECT/CT.  Iodine is not the best isotopes to image with and with high energy collimators, it would have been tough to identify based on static images.

Therasphere Part Deux

Our first patient, who has a long standing history of hepatocellular carcinoma (HCC), was excluded as a surgical candidate to remove the tumour in the right lobe of the liver because the patient suffers from portal hypertension and low platelets.  The alternative consideration was for transcatheter arterial chemoembolization (TACE) to treat the tumour,  however somehow this patient ended up in the trial study of Yittrium-90 Theraspheres at our facility (click on link for further reading)

A mesenteric angiography and embolization was performed as the first step of the selective internal radiation therapy.  The reasoning is to ensure the blood flow localizes into the tumour site while sparing normal healthy sites when the Y-90 is delivered.   The mircocatheters where inserted through the right femoral artery and threaded to the right hepatic and left hepatic arteries for the arteriography.  The right gastric artery, which arose from proximal left hepatic artery, was embolized with vortex coils.  Furthermore the gastroduodenal artery was emoblized as well, leaving patent the common hepatic artery, the left and right hepatic arteries.

Fig. 1  Infusion of contrast through the right hepatic artery.  Note the embolization coils below.

Fig. 2  Infusion of contrast through the right hepatic artery, outlining the tumour in the right lobe.

Fig. 3  The right lobe tumour is now fully visualized, with limited shunting.  However there is still extraneous vascularity.  Thus the lung shut fraction is calculated to quantitate the amount.

After the embolization process, Tc-99m MAA was injected through the microcatheter for the lung shunt study.  After the injection, the patient was stabilzed for transport to Nuclear Medicine, and the following images were taken.

Fig. 4  Anterior and posterior images were taken to determine any major shunting of blood to the lungs or stomach.

Fig.  5  Regions of interest were drawn over the lungs and liver and a geometric mean was calculated to determine the lung shunt fraction (LSF).

Lung shunt fraction was calculated to be 3.0%.  There is no cut off with regards to the LSF value to be excluded from the treatment.  However it is the discretion of the interventional radiologist who will be administering the Y-90 to determine the patient's inclusion within the treatment study.

Two weeks after the initial angiography and embolization, the Y-90 theraspheres were adminstered.  Based on the size and volume of the tumour which the interventional radiologist calculated prior to the administration, we wanted to give approximately 2.5Gbq of Y-90 to deliver 120Gy to the tumour site.

Nordion which supplies the theraspheres, has an excel worksheet to help with the ordering of the Y-90 dose to ensure the proper calibration of the actual dose.
In the end, the amount that we calculated (approximation) of the dose delivered to the tumour site was about 2.49GBq, based on a 1.7% residual activity remaining in the Y-90 administration vial.  Overall the tumour received 120.7Gy with the lungs receiving approximately 3.73Gy, based on the LSF value.

Having worked through our first patient it is important to address the fact that most Nuclear Medicine technologists are accustomed to working with radioactive materials.  However the interventional radiology (IR) technologists and some IR doctors do not.  The dose rate is quite high with respect to the Y-90 vial.... but we normally do not tell them how high it really is.  Thus it is a good idea that you get them on board with respect to working with radioactive materials and how to handle these materials without causing too much of a mess.  The reason why, is that they are most likely going to set up the Y-90 administration set, since they have much more experience than Nuclear Medicine technologists in a sterile field.  Plus it will be the IR doctors (at least at our site), that will be injecting the Y-90.

Fig. 6  An unassembled administration set.  Everything is performed in a sterile field.  I will endeavour to update this image, once everything is connected together, when our next patient arrives.  Which should be in 2 weeks time.

Theraspheres

Just got back from Chicago... (fun town), on a training seminar in regards to TheraSpheres.  For those in the United States and Europe, this might be routine practise in treating liver cancers (hepatocellular carcinoma HCC), but not so much here in Canada.  There are only a few places in Canada that are performing these procedures (BC, Alberta) but not sure what type of volumes they have in regards to this type of treatment.  The Nordion sales reps have stated that they have some type of involvement within these regions.

At any rate what is a TheraSphere?  They are glass beads with Yittrium-90 attached to the surface.  The beads themselves are biocompatible and insoluble and have a mean size between 20 - 30um.  These beads are injected through a femoral line while undergoing a hepatic angiogram in Interventional Radiology (IR) and the beads are deposited close to the site of the liver lesion that you want to treat.

What's tricky about this is, figuring out the blood supply to the region of the liver in and around the tumour site(s).  For the most part the blood flow to the liver is fairly predictable, but with respect to some patients it's a bit more complicated because of a variety of arterial variants, parasitization of flow, accessory arteries, retrograde blood flow etc. that if not found with a thorough investigation, the deposition of the TheraSpheres will not go entirely to the tumour, but elsewhere within the body.  This is not a good thing, since adverse reactions may potentially occur.  The case studies illustrated these quite well at the training seminar.  However, for the most part Yittrium-90 radioembolization of the HCC tumours has several advantages in that it has a lower toxicity profile in comparison to transarterial chemoembolization.

So what does TheraSpheres have to do with Nuclear Medicine?  Well for the most part we assay and deliver the Yittrium-90 to the angiography suite, and from there the IR techs and the IR doctors take care of the rest with respect to the injection and the clean up.  This will vary from site to site, depending upon the level of comfort and training in dealing with radioactive materials.

However even before this occurs, Nuclear Medicine is important in determining extra hepatic shunting to the lungs or gastrointestinal tract as part of the selection process in figuring out who are good candidates for this treatment.

150MBq of Tc-99m MAA is injected with a microcatheter into the hepatic artery after coil embolization of all visible non hepatic arterial flow.  Basically, whatever blood flow that doesn't deal with the liver, they get clamped down with coils, in order to figure extrahepatic flow.  The image below is an example of this type of imaging.

Fig. 1  ROI's drawn over the lungs and liver to determine the counts for geometric calculations to determine the Lung Shunt Function (LSF)

Anterior and posterior images are taken to determine regions of interest (ROI) to find out the Lung Shunt Fraction (LSF).  The geometric means are calculated from the lungs and liver using the numbers from the ROI's  and are used in this equation:

LSF = Lungs / (Liver + Lungs) *100

The reason why this is important is because it helps in determining the dosimetry calculations for pre and post treatment.  This is important since you need to know how much radiation to give given a specific volume of liver that you plan to treat without affecting other parts of the body (ie. lungs).

There is the question of planar versus SPECT/CT imaging with MAA.  At the training seminar, planar imaging was described, but others have suggested performing SPECT/CT.  Since at our site we have limited experience with this protocol, we would need to speak to the IR doctors and the Nuc Med doctors to figure out what they want.

The current imaging protocol for Tc-99m MAA:

Static Imaging Protocol (Northwestern Hospital, Chicago):

Dosage:

- 37 -185 MBq Tc-99m MAA, injected in IR and the patient delivered to Nuclear Medicine

Equipment:

- Any large FOV dual detector gamma camera, with LEAP or LEHR collimation

Imaging:

Option 1:  The patient is positioned supine under the gamma camera and 4 images are acquired.  Anterior and posterior images of the abdomen and of the thorax are acquired separately

Option 2:  The patient is positioned supine under the gamma camera and a whole body scan is acquired

Camera Parameters:

- Acquisition matrix = 256 X 256

- Zoom = 1.45 or less to ensure all activity visible in FOV; total counts >1M

- Counting time - 5mins per 74 MBq administration of Tc-99m

SPECT/CT Imaging Protocol (University Hospital Essen, Essen)

Dosage:

150 MBq Tc-99m MAA

Equipment:

- Dual headed gamma camera, with SPECT/CT capability

Imaging:

- 30 minutes post injection of Tc-99m MAA, anterior and posterior planar images of the whole body 

- SPECT/CT afterwards

Camera Parameters:

- SPECT - 128 X 128 matrix

- 128 frames (25 secs/frame)

- CT - 130 keV, 17 mAs, 5mm slices

There is also talk about PET/CT imaging as well.  Since Yittrium-90 is a beta emitter, having the patient come back the following day after treatment allows imaging of the distribution and deposition of the microspheres within the body.  

Anyway, there is a lot to know about this procedure and I am only scratching the surface. At our facility we have had some experience with this many years ago, but now there is a real push with some of the doctors at the hospital to revisit this type of treatment again.

Stay tuned........

Update:  Check out Theraspheres Part Deux, in this blog site.  We've performed out first LSF and treatment.

Certification Exam - Student Questions

It's going to be busy the next couple of weeks, since most of the students will be cramming for their certification exam.  I've been working on a few cases but haven't posted up anything just yet... so sorry about that, BUT to replace the case studies I will be posting the questions posed by the students to help them study for their exam.  

Q1.  If a breastfeeding women just had a bone scan, do you tell them to stop breastfeeding for 24 hours? Where do I  find the correct interruption times for all the radioisotopes??

A1.  According to the literature, there is no cessation of breast feeding for mothers who just had a bone scan.  However, other radioisotopes like Ga-67 requires at least 1 month, but this effectively stops any type of breast feeding since there will be latching issues later on.

References:  

1.  http://www.pciphysics.com/docs/BreastFeedingDelayChart2009.pdf

2.  http://nrc-stp.ornl.gov/narmtoolbox/nureg1556vol9_rev2_012408.pdf  (see Appendix U, page U-9)

3.  Journal Nuclear Medicine, vol 41 p. 863-873, 2000