I'll Be Back - 2014

Sorry... I have been neglecting my BLOG.... not really, but I have some interesting cases to post for the students.  Just getting the time to work through the cases is difficult - but I'm still keen.

My last post was March 2013... shame, I know.  My New Years resolution is to update this Blog on a regular basis, since in the New Year I'll have some flexibility in developing educational content for the school that I am moonlighting with now.

Fig. 1  Here is something that we do not see very often.  Really interesting location for lymphoma.  I assure you that this was not from a spill practical training course.

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.

PET Melanoma

Needless to say this patient presented to our department with late stage melanoma.  A new lung nodule had presented itself on the right lung from a chest x-ray and a PET/CT study was ordered and performed according to departmental protocol.

The patient has had extensive surgery to remove the melanoma from the lower back, along with excision of lymph nodes.  The patient also had a previous bout Bowen's disease over the right breast with further metastasis to the left axillary nodes.  Upon follow up with the medical oncologist, post surgery, a chest x-ray was performed and it noted a right solitary lung nodule.  

The PET/CT was performed and the following images demonstrate extensive and diffuse metabolically active metastatic adenopathy, as well as skeletal, pulmonary, liver, splenic and small bowel metastases.

Fig. 1  Multiple foci of metabolic activity of F18-FDG

Fig. 2  Sagittal fused image of the patient, noting multiple F18 FDG uptake in the spine

At our facility for indications of single pulmonary nodule (SPN) or for non small cell carcinoma (NSCLC) we normally scan from the top of the head to mid thigh.  If they have had a previous MRI of the head to determine brain metastases, then we will scan from the base of the skull to mid thigh.  However in this case, the patient has had a previous history of melanoma, we decided to scan from the top of the head to their feet.  This is our normal protocol with regards to melanoma patients.  Basically we performed our melanoma protocol on the patient referred for a lung indication.  

Generally it takes about 30-35 minutes to scan from the top of the head to their feet depending on the height of the patient.  Considering that our PET/CT is an old Seimens Biograph with a 2 slice CT, it does take up a bit of time with respect to the CT acquisition.  In addition to this, we do not have the the time of flight (ToF) capabilities to decrease our acquisition times of our PET.   However, we are replacing our Biograph with a new machine, since the 2 slice Biograph has come to the end of life for servicing.  Anyone interested in a PET/CT unit for training or for a back up?

Adrenal Hyperplasia and PET/CT

Fig. 1  Coronal CT image.  Note the "inverted Y" shaped tissues just above the kidneys.  This is what typical adrenal glands look like on CT.  Click on the link for more in depth information.

Fig.  2  Same section of the coronal plane corresponding to the previous CT.  Note the F18 FDG uptake above the renal poles, midline to the body.

Fig. 3  Fused CT and PET image of the two images.  Note the metabolically active regions above the poles of the kidney, midline to the body.  Expand the image to get a closer look.

Generally, PET/CT requisitions must be approved by our physicians and they have to follow certain guidelines for approval as set out by local government who sponsors some of the costs.  However some patients do not fall within these guidelines and as the result they must go through another route.  Well this is one of those patients that have gone through this "other" route to have their scan.

The case history is interesting.  Originally the patient presented with fatigue and proximal leg weakness with a long history of hypertension and dyslipidemia.  However, recently the hypertension has been uncontrollable and had developed hypokalemia, weight gain, bruising,  and diabetes.  Blood work was also performed to correlate these findings (dexamethasone suppression test).  To make a long story short, they suspected that Cushing's Syndrome may be the cause.  

Cushing's Syndrome tends to be rare often affecting maybe 2 to 4 cases per million inhabitants  per year.  The problem with this condition is that, there is too much glucocorticoids being produced by the adrenal glands (adrenal cortex), in particular cortisol.  Cortisol affects the body's pathways in the following:

1.  Stimulates gluconeogenesis in the liver

2.  Mobilization of amino acids from extra hepatic tissues to act as substrates for gluconeogenesis

3.  Inhibition of glucose uptake in muscle and adipose tissue to allow for glucose conservation

4.  Stimulation of fat breakdown from adipose tissue.  Basically the fatty acids are used for energy production in tissue (muscle) and the glycerols from the fat are used for other substrates for gluconeogenesis

The glucocorticoids have an immune and anti inflammatory response as well, often given in therapeutic doses to treat arthritis and dermatitis.

So how do you produce too much glucocorticoids?  There are a couple of ways:

1.  The negative feedback loop among the hypothalamus, pituitary gland and the adrenal glands do not work.  Basically there is too much adrenocorticotropic hormone (ACTH) being produced by the pituitary thus influencing the adrenal glands to produce more glucorticoids

2.  There is/are tumour(s) within the adrenal glands

3.  There is/are ectopic tumour(s) elsewhere in the body producing cortisol

4.  There is/are ectopic tumour(s) elsewhere in the body producing ACTH

Getting back to this case, the patient had a "radiological work up" to figure out what was wrong.  The ultrasounds did not give any indication of any tumours in the adrenals but the initial MRI had discovered a micro adenoma on the anterior pituitary which may have contributed to the increased ACTH levels in the system.  Consultation with the patient began to remove the adenoma in the coming months.  

Once the micro adenoma was removed, the patient had some of the symptoms go away, but they had returned a couple of weeks later.  Another series of radiological work ups were performed to figure out if an ectopic source could be the cause.  A CT scan was performed and again no adrenal tumours were found and other gross anatomy were unremarkable.  It was at this point that the clinicians decided to come and see us in the PET/CT department.  It was basically to assess any remnant tumour(s) in the pituitary as well as any potential ectopic lesions in the rest of the body.

The PET/CT scan was negative for residual activity in the head and neck region (images not posted), nothing metabolically active in the chest, but in the abdomen there was bilateral diffuse uptake in the adrenal glands, with a maximum SUV value of 4.6 (see Fig. 2 and 3)  There was also smooth thickening of the adrenals which correlated with a previous CT scan.  Even though there wasn't any other discoveries of ectopic sources, the information presented by the PET/CT suggested of an underlying adrenal hyperplasia that may be contributing to the patient's recurring symptoms.  Here are the transaxials from the study.

Fig. 4  Transaxial CT slice.  Note the adrenals (beside the descending aorta) and slightly above the renal poles.

Fig. 5  Bilateral metabolic activity towards the midline of the image corresponding to the CT slice in Fig. 4. 

Fig. 6  Fused image depicting bilateral adrenal gland activity.

Overall the adrenal glands do not regularly show up on the PET/CT scans and only become so when they are overtly over active.  I have only been able to find a handful of articles that describe this metabolic appearance. 

However, from a general Nuclear Medicine perspective, adrenal gland imaging can be performed using iodine labeled radiopharmaceuticals, such I-131 NP-59 for adrenal cortical imaging and with I-131 MIBG for adrenal medullary imaging.  To improve imaging with MIBG, I-123 can also be used as well.  The I-131 NP-59 imaging was not performed in this case since this is not readily available in Canada due to restrictions from Health Canada.

Cardiac PET/CT

Cardiac imaging is a main stay within Nuclear Medicine in particular myocardial perfusion imaging which are often used to screen for acute coronary syndromes and the presence or absence of arteriosclerosis.  The more common isotopes used within Nuclear Cardiology are Thallium-201, Tc-99m and F-18.  Obviously other isotopes exist such as C-11 and N-13 for myocardial metabolism, but at our facility we generally stick to the "bread and butter" stuff.

The main focus of this section is on F-18 FDG cardiac imaging for viability.  Yes, Thallium-201 has been the champion of viability imaging for many years, but with the increase interest, the approved reimbursement (partial) of FDG cardiac imaging by the government and better imaging characteristics with PET, it is starting to catch on.

The imaging aspect of the myocardium is fairly straight forward with respect to PET/CT, since gating is not involved.  The tricky part is patient preparation to obtain good myocardial uptake of FDG.  We have had scans where the myocardium did not appear to have FDG uptake.  Needless to say, there was something amiss with the preparation.

Fig. 1  CT only, left ventricle.

Fig. 2  Fused PET/CT of the left ventricle.

Fig. 3  F-18 FDG AC of the left ventricle.  PET image only.

Why do we perform myocardial PET/CT scans in the first place?  

The rationale is to determine cardiac viability within patients with left ventricular dysfunction to figure out who will benefit from a re-vascularization procedure.  It is to find a better way to screen patients from those who will benefit from re-vascularization versus those who will not.  This really centres around the presence or absence of a "hibernating myocardium".  The PET/CT scan is compared to the patient's baseline Tc-99m sestamibi scan to see if there is an increased uptake of FDG in the region of the left ventricle where the defect is present (MIBI scan).  If there is an increase in FDG uptake, it suggests that a "hibernating myocardium" is likely, and if there is no FDG uptake the region in question is more likely to be a myocardial scar.  Thus the course of action is much simpler for the clinician with this type of information.

How do we prepare the patient to optimize the scan?

There are a variety of protocols, but the basic premise behind all of them is to drive the FDG into the myocardium.  The tricky part is usually working with diabetic patients and dealing with the blood glucose levels during the prep.  

Non Diabetics and Diabetics (oral glucose load)

-Patients fasting for 6-12 hours, minimum 6 hours

-Hold oral diabetic meds/insulin, if fasting overnight

-Diabetic patients are scheduled in the morning

Baseline blood glucose measurement (BGM) is taken, and depending on the level measured (mmol/L) there is a sliding scale in the amount of GLUCOLA (GLUTOL) - a very sugary drink, that is given.  If the initial BGM is lower than 5 mmol/L, then we give 50g of Glucola, if the BGM is higher than 5 mmol/L, then we give less of the drink, and if the BGM is really high we give the drink and a shot of insulin - yum!

1 hour post sugary drink, we get our second BGM, and again we have a sliding scale on how much insulin we should inject based on the measurement.  If the BGM is around 7.2 mmol/L, we give 1 unit of insulin, but if the BGM is higher in the 8 mmol/L - 11.0 mmol/L range, than higher units of insulin are given.

Injection of F-18 FDG is given during this time as well.  After the injection, there is a wait time anywhere between 45 - 60 minutes before the PET/CT scan is performed.

Diabetic Patients (insulin - glucose infusion)

-Patients fasting for 6-12 hours, minimum 6 hours

-Hold oral diabetic meds/insulin, if fasting overnight

-Diabetic patients are scheduled in the morning, but if they are scheduled for the afternoon, breakfast and medication as required

Baseline BGM.  If it is greater than 10 mmol/L, may require an insulin bolus before starting the insulin - glucose infusion.  Generally the insulin infusion is started first then the glucose afterwards, but if the patient had a low BGM initially the glucose would be infused first and then followed by the insulin.

Injection of F-18 FDG usually occurs when the patient's BGM stabilizes and or begins to decrease.  The ideal scan occurs around 5 mmol/L, but most times we are happy with the BGM dropping and stabilizes to an acceptable level.

PET/CT scan usually starts anywhere from 45 - 75 minutes, we generally try to keep it consistent between 45 - 60 minutes.  The insulin - glucose pumps do not go into the scan with the patient, they are disconnected and monitoring of the patient continues post imaging.

F18-FLT PET/CT Imaging

FLT = [F-18] Fluorothymidine

FLT is a unique PET tracer in which it targets cellular proliferation, the rate of DNA synthesis, in patients to evaluate the effectiveness of anti-neoplastic drugs affecting DNA replication.  The thymidine component of the FLT does not actually get incorporated into the DNA replication process because of a phosphorylation event creating an ionic FLT-MP (monophosphate).  It is FLT-MP that gets trapped within the proliferating cells.

Majority of the patients that we see are already on their cycles of 

anti-neoplastic treatment when imaging with F18-FLT.  Normal 

bio-distribution of FLT includes the bone marrow, lymphoid tissue, kidneys and bladder.

Imaging with FLT is no different than FDG, except for the fact that the injected dose is based on 3MBq/kg rather than 5MB/kg with respect to FDG.  At least at our institution. The post injection imaging time is still relatively the same, approximately 60 minutes +/- 10 minutes however it is not necessary to obtain blood glucose measurements since the mechanism of action is different than that of FDG.

A Picture Says a Thousand Words

Basically every time we perform a PET/CT scan, there are a few questions we like to ask the patient.  Namely whether if they are a diabetic, and if they are, what time did they take their insulin or hyperglycemic medication.  The other thing is, have they eaten anything within the past 6 hours.  Given the image above, what do you think happened?  Does this look like a typical PET scan using F18-FDG?

Indication:  Thyoma PET study

Findings:  Paitent did not prepare for the PET/CT examination, a follow up study is required.

Hx:  The thyoma study requires the patient to undergo presurgical radiation therapy and chemotherapy, in the attempt to increase the chances of a complete resection.  The PET/CT scans are done prior to the chemo and radiation therapy and then post surgery.  The PET scans are performed 3-4 weeks post treatment to avoid reactive responses causing false positive scans.

With this case, the PET/CT scan was performed post surgery.  The patient during the screening process denied eating prior to the test.  The blood glucose measurement did not suggest otherwise, however upon completion of the exam, the image included vast muscular uptake.  The patient confessed in having a coffee and a muffin 1 hour prior to his PET/CT injection.

Three days after the scan above, another PET/CT scan was performed.  Compare the difference.  It's not great but definitely improved.