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.

In-111 Pentetreotide Imaging

I have had a lot questions with regards to In-111 pentetreotide imaging by my students since we have block bookings once a month to accomodate some of the physicians' requests for these scans.  Sometimes when I start talking about somatostatin and somatostatin receptors I get this glazed look in their eyes.

The best place to start would be to look at the Society of Nuclear Medicine procedural guidelines (SNM), since it would provide a grand overview of what this type imaging is all about.

We need to make the distinction between pentetreotide versus octreotide when discussing the imaging aspects, however.  In nuclear medicine the In-111 pentetreotide is the compound that we work with, because it has a DTPA chelator attached to it to allow it to bind to the indium-111 isotope.  Essentially pentetreotide (In-111-DTPA-D-Phe) is a conjugated form of a somatostatin analog.  Octreotide on the other hand is just a peptide (an octapeptide to be exact) that mimics the natural somatostatin that is found within our bodies.  Basically, octreotide is a synthetic version of the natural ones within our bodies.

Fig. 1  This is the pentetreotide peptide.  For those who would want to know what it looks like.

Fig.  2  This is the structure for Octreotide.  I will say this:  I am not a radiochemist, or a radiopharmacist and I did not take organic nor inorganic chemistry.  However, I made sure our radiopharmacist was okay with these images before posting.

Here are some images that we have acquired recently.  It will help us with the discussion.

Fig. 3  A 24 hour In-111 pentetreotide scan of a patient with gastrinoma.  Notice a focal uptake in the midline of the body, along with a faint uptake in the liver.  You can see it better in the whole body images on the right.

Fig. 4  Another 24 hour whole body imaging.  Note the focal uptake in the midline of the body.  This patient was being worked up for insulinoma.

Fig. 5  As above, imaging was performed at 24 hours.  However note the uptake in the thyroid.

Majority of the patients that come to see us receive an In-111 pentreotide injection for some type of neuroendocrine imaging.  Most of them involve the gastroenteropancreatic (GEP) tumours such as the insulinomas, gastrinomas, VIPomas (vasoactive intestinal polypetide secreting tumour) and other times we get the occasional request for carcinoids.  

Patient preparation is fairly straight forward, but one thing that is interesting is the decision to infuse glucose in patients in those suspected of insulinoma.  This is to prevent the potential problem of hypoglycemia during the injection.  It is not common practise and it is the decision of the radiologist to incorporate this in their standard of practise with these cases.  We do not do it at our site.  The one thing that we do screen for are medications, such as the use of Octreotide as a therapeutic agent.  Since Octreotide is the synthetic form of somatostatin within our bodies, it's more potent and effective in suppressing gastrin, cholecystokinin, glucagon, TSH, pancreatic polypeptide, secretin, growth hormone, TSH and vasoactive intestinal peptide.  Careful consideration of the time when the patient had taken the Octreotide is important as we want to ensure good uptake of the In-111 pentetreotide.  More patient preparation information can be reviewed in the SNM guidelines, or in the European Association of Nuclear Medicine guidelines as well.

The imaging of these patients are fairly straight forward as well.  Whole body scanning is generally done at 24 hours, but before when we had purchased our SPECT/CT, the standard of practise was to perform whole body imaging as well as, a standard SPECT at 48 hours.  The SPECT/CT was a bit of a game changer for us, since our radiologists were comfortable with the images obtained at 24 hours that included the SPECT/CT.

Not all these tumours are created equally.  In order to be visualized they require a number of somatostatin receptors on the tumours themselves. There are 6 known receptors:  SSTR1, SSTR2a, SSTR2b, SSTR3, SSTR4, SSTR5.  Note there are also subtypes as well.  With the "lock and key" method of visualization, the sensitivity of the tumours will vary.  For example, there is better sensitivity in gastroenteropancreatic neuroendocrine tumors (download the PDF, it's free), except for insulinomas as the result of the lower incidence of somatostatin receptors, especially those of the SSTR2.  The sensitivity is approximately 25-60% in comparison to the other tumours in this category.  The best practise for our department is that our radiologists screens the requisitions before we begin the bookings and the ordering of indium-111 for compounding.  

I want to touch upon one thing however and it is the biodistribution of the In-111 pentreotide.  Generally the normal uptake of In-111 pentreotide occur in the pituitary glands, the thyroid, liver, spleen, kidney, bladder and sometimes gallbladder.  Bowel is also seen but more so after 24 hours post injection.  If you look at Figure 5 in comparison to the other images, there is the obvious uptake in the thyroid bed.  I personally have not seen this very often, so my initial inclination was "abnormality" since medullary thyroid cancers and pituitary adenomas express high amounts of somatostatin receptors.  Upon reviewing the finalized report, it did not mention the uptake in the thyroid bed, but rather indicating no evidence of any octreotide avid pancreatic tumours or metastases; the biodistribution was normal.  Further review into the patient history, just recently, had the patient to undergo an urgent thyroid ultrasound and aspiration for pre-op staging.  This patient had a previous biopsy of the left thyroid as well, but it had unsatisfactory cellularity in the sample for any type of determination.  The CT work up report for this patient also noted a left thyroid nodule.

I'm not aware of any recent results in regards to the identification of the nodule, but this is something that I will be following up for my own education.  This may be a potential occurrence of an incidental finding for thyroid carcinoma.... who knows?

Ewing's Sarcoma

Sorry about the long hiatus, but here is something that came up a couple of weeks ago which was a bit tragic for the patient, but at the same time quite an interesting case.

I personally have not seen a gallium whole body scan like this, and likewise with the other technologists in the department.  This patient was being worked up for Ewing's sarcoma.  

When the patient arrived in our department, they were in a considerable amount of pain.  We limited the SPECT/CT to only 1 bed as oppose to our regular whole body SPECT/CT which covers 2 to 3 bed positions on our Symbia T6.  Having said that, it was quite obvious where the tumour was located.

Fig. 1  Ga-67 whole body image of a patient being worked up for Ewing's sarcoma.  The right  thoracic area has intense gallium uptake.

The right thorax contained majority of the gallium uptake, with little evidence of metastases outside of the area.  However, the CT demonstrated a much clearer extent of the disease involvement with the spine and the surrounding bony structures.  The patient originally was asymptomatic, but as the disease started to spread, a rapid loss in weight occurred and discomfort emerged from the right posterior region of the back.

Fig. 2  Transaxial CT slice.  Notice the periosteal reaction in the posterior rib and spine.

Fig. 3  Sagittal slice with an almost complete opacification of the right lung.  Most of the lung has collapsed due to the right sided mass and effusion.

Fig. 4  A coronal slice further depicting the multiple lytic changes in the right sided ribs as well as the invasion of the tumour into the spinal canal.

Overall the disease state was quite extensive with an extra large parenchymal mass filling up much of the right hemithorax, measuring up to 13 cm in thickness.  The disease may have started in the spine or in one of the ribs and over time became invasive.  A further MRI of the spine was performed to assess the spinal canal and spinal cord as the patient began to have bilateral leg weakness and tingling in the feet.

Generally with Ewing's sarcoma it often occurs during childhood and can start anywhere in the body.  However it tends to target the long bones, that are hard, dense bones that provide strength, structure, and mobility.  Almost a third of the patients have some metastases to other locations, generally to the lungs and in to other bones.  Click on the above link (Ewing's sarcoma) for more information.

Takayasu Arteritis and PET/CT

Takayasu arteritis is one of the indications that we perform an F18 FDG PET/CT scan on, primarily as a research protocol.  This is one of those research studies that we do not do very frequently but once in awhile they pop up on our list.  

What is interesting about this condition, besides the name, is that this is a rare condition that causes vasculitis in the large vessels, such as the aorta and it's branches.  

The history of Takayasu arteritis is pretty interesting as well.  Originally this vascular disease was reported by Dr. Mikito Takayasu, an ophthalmologist in 1908 at the 12th Annual Meeting of the Japan Opthalmology Society. It basically came about with the appearance of "coronary anastomosis" in the eyegrounds and arteriovenous anastomosis around the papila of a 21 year old woman that Dr. Takayasu was examining.  Further investigation lead others to report "pulselessness" in their patients which is another clinical feature.  The radial, brachial and carotid pulses are absent in these patients as the result of the ischemic cerebrovascular circulation.  There's more, but if you click on the link at the start of this paragraph, you can read the rest.

So here is what it looks like in PET:

Fig. 1  FDG PET imaging of a patient with Takayasu arteritis.  Abnormal increased activity are identified along the brachiocephalic and proximal right and left common carotid arteries.

Fig. 2  A fused image denoting the areas of uptake with anatomical features.

Fig. 3  Sagittal fused image with uptake through the common carotid artery.

The preparation for the Takayasu arteritis scans are fairly similar to the other oncological preps that we do in the department except for the fact that we scan with the arms down, we wait for a 90 minute uptake (since the appearance of the inflamed arteries are very subtle thus maximizing the uptake time is essential) and we use an ideal body weight (IBW) calculation.  The cut off glucose measurement is around 11.0mmol/l.  This is slightly higher than the normal cut off of 9.8mmol/l for the rest of our scans.  Imaging is taken from the base of the skull to mid thigh, but 4 minutes per bed for the PET as oppose to the 3 minutes per bed with most of our oncological studies.

As you can see in Fig. 1, there is abnormal increased activity identified along the brachiocephalic and proximal right and left common carotid arteries.  There is also increased activity in the descending aorta at the L2-L3 vertebra, which I did not capture on my screen shots.  PET/CT would probably not be the first choice in terms of imaging with a suspected case of Takayasu arteritis, the more likely options would be CT angiography or MRI to examine the nature of the large vessels.

Sarcoid versus Scleroderma

I always get mixed up when it comes to sarcoids and sclerodermas when written on a requisition.  Currently we perform imaging on these patients to help the clinicians to determine the extent of their patient's disease, but I still get confused as to the nature of the disease and their processes.  So this portion of the blog is partly to help me and anyone out there that are in the same position.  I have tried to put this into a chart format, but it doesn't translate well into the blog.

Sarcoid:
This is an inflammatory disease that can potentially affect multiple organs within the body.  It most often starts within the lungs or lymph nodes, but it does not limit it self to these areas.  The inflammation (sarcoidosis) is not necessarily caused by an autoimmune response, since this is not an autoimmune disease, but the cause of this inflammation is uncertain.  The most distinguishing feature about sarcoids is that they deposit granulomas (microscopic lumps of inflammation).  They sometimes clear up on their own or they can become fibrotic if they remain in the body if they do not heal.

The most famous entertainer to die from sarcoidosis was Bernie Mac.  His condition was primarily localized to his lungs, but sarcoids, like I mentioned before can affect any organ.  Here at our facility we image and follow these patients when they become part of the CADRE study.  CADRE represents the Cardiac FDG-PET Registry Study.  As part of the cardiac program, we look at the extent of their disease via a whole body PET/CT, which we append to their Tc-99m myocardial perfusion studies.  Along with the whole body PET/CT, we will perform a quick FDG viability study of their heart while in the department.  Most of these patients have their cardiac workup prior to coming to PET.  Approximately 25% of all sarcoids involve the heart, and about 13-25% of all sarcoids deaths are related to cardiac insufficiencies such as heart failure, ventricular tachyarythmia or conduction disturbances.

Fig. 1  Extensive uptake of FDG within the thorax, liver, spleen and both kidneys, correlating with the patients known sarcoidosis.

We also perform gallium-67 whole body imaging to localize the areas of inflammation, in particular the lungs.  But quite honestly, we do not perform these routinely, and having said that, I don't think I have ever seen one that was positive.

UPDATE January 2, 2012:  I will take back that last comment about not seeing a positive gallium scan for sarcoidosis.  The image below was taken 48 hours post Ga-67 injection.  A whole body gallium scan was performed and there was uptake within the lungs consistent with sarcoidosis.

Fig. 2  Uptake in the hilum and the lungs, consistent with sarcoidosis

Scleroderma:
This is the result of inflammation in connective tissue featuring the formation of scar tissue (fibrosis) in the skin and organs of the body.  Scleroderma is an autoimmune disease, as the result of an overactive immune system.  They have specific antibody markers such as ANA, anticentromere or antitopoismerase in their blood stream which suggests autoimmunity.

We perform gallium imaging for scleroderma, but rarely.  I have not come across this condition with regards to the patient's history for PET/CT imaging.... yet.

I do not have any images to show from our facility and there isn't much on the web either.

Unusual Gallium Localization - B-Cell Lymphoma

Fig. 1  Post 72 hour whole body gallium imaging for a 74 year old patient, with B cell lymphoma

Gallium scans, in general, are fairly routine in helping clinicians to understand the extent of certain lymphomas in their patients.  For the most part PET imaging is the standard of care in many parts of the world, but with limited access to this type of imaging in certain provinces, we still rely on gallium (ole faithful).

What is interesting about the image above is the location of the gallium avid tumours.  I personally have never seen uptake in the actual arm itself.  The images above describes the uptake in the right infraclavicular lymph nodes, right axillary lymph nodes, soft tissues lateral to the mid shaft of the humerus and soft tissues posterior/lateral to the distal shaft of the humerus.  A SPECT/CT was performed, which included the arms and thorax.  The sagittal slice reconstruction below helps in clarifying the location of the tumours in the arm.

Fig. 3 Sagittal reconstruction of the right arm localizing the  gallium avid tumours.   The  video below is the 2-bed SPECT scan of the patient.

The patient initially presented with anemia.  Upper and lower gastrointestinal investigations did not reveal anything out of the ordinary, but the blood work for hemoglobin, mean corpuscular volume (MCV) and ferritin results were abnormal. The lumps and nodules in the right arm have been present for 8 years, and it was only recently that they began to grow in size, but were not painful.  The patient was diagnosed with diffuse B cell lymphoma and is currently undergoing treatment.

Burnt Out

Top:  Anterior feet (detector 1); Bottom:  Posterior feet  (detector 2)

What's wrong with this picture?  

First off, this is an In111-WBC scan to localize infection in the ankle.  The top image is the anterior view (detector 1) and the bottom image is the posterior view (detector 2).  What is interesting is that there is a "bite" taken out of detector 2.  As you know, this is probably not something that you would want in your image, but rather a technical artifact in which a photomultiplier tube has burnt out during the image acquisition.

There are 2 things to discuss here:

1.  White Blood Cell (WBC) scans:  

The decision to use Tc-99m WBC versus In-111 WBC is based on the a decision tree approved by our physician.  It really revolves around whether the patient is diabetic and or has a prosthetic or implant post surgery.  With WBC scans, it's primarily used to determine infection such as osteomyelitis, which for the most part represents 99% of our cases.

a.  Not diabetic or no implant - Tc-99m WBC

b.  Diabetic with (?) foot infection and/or has prosthetic implant - In111-WBC 

All WBC cases have a bone scan first followed by either the Tc-99m or In-111 WBC scan afterwards.  The one main thing to note is that if the In-111 route is taken, they are given Tc-99m sulphur colloid first before the In-111 WBC injection on the same day to determine if there is any bone marrow involvement with the site in question.

Having said this, I have yet to see a positive scan to date.  The current case above was to determine post surgical infection of the right ankle.  The scans for both the sulphur colloid and the In-111 WBC were unremarkable, but there were post surgical changes on the right distal fibula and ankle (image not shown) on the bone scan.

What about gallium?  At our site, gallium is not the isotope of choice unless discitis is indicated.  In-111 WBC's are not as effective in relation to Ga-67 in conjunction with a bone scan, to determine discitis/vertebral osteomyelitis.  Accuracy for WBC's are generally low for this type of imaging (Henkin et al. Part IV p. 1129)

2.  Photomultiplier tubes (PMT)

Basic premise with PMT's are to convert light into an electrical current.  There are a multiple of reasons why PMT's burn out.  Daily quality control and monthly preventative maintenance programs are important to detect these irregularities.  PMT's have been around for many years, but with new solid state cameras like the CZT (Cadmium Zinc Telleride) equipped systems, PMT's may be a thing of the past.  Who knows?

Whole Body Gallium - Lymphoma

Contrary to most standards of practise, gallium-67 whole body imaging is still being performed for neoplastic staging of lymphomas.  Many centres have now moved away from this and use F18-FDG as part of their protocol.  However having said that, a whole body scan along with a four bed SPECT/CT was performed to aid in the staging process.

Indication:  Staging of neoplasm.  Lymphoma of the left tibia.

Findings:  Intense gallium avid lesion in the left proximal tibia and fibula, corresponding to a know bony lesion at this site.  Further gallium avid activity are localized in 3 sites on the left parietal region of the skull, along with another foci of activity in the left parietal skull.  In addition, abnormal gallium activity is found midline to the abdomen below, but separate to the transverse colon.  No other soft tissue abnormality is observed.

Hx:  Imaging with gallium-67 has been around for almost 40 years, first described by Edward and Hayes in 1969 (J Nucl Med. 1969;10:103–105).

It has been used in a variety of indications such as inflammation, infection and tumour localization (osteosarcomas, lymphomas, testicular tumours, melanomas), but for the most part, gallium has been used in oncology to stage and monitor the response of tumours to treatment.

With regards to imaging, most patients are scanned 72 hours post injection. Encouraging them to drink lot's of fluids within the first 24 hours is done to eliminate gallium from the genitourinary system, afterwards the patient may take a laxative to help in eliminating the gallium through the bowels.

Upon 72 hours, a whole body gallium image is taken.  Depending on the clinical site, the arms may be raised to allow better visualization of the axillary regions or they may be left down by their side.  SPECT/CT is also used afterwards to improve the specificity and sensitivity of the study.