Clinical Applications in Nuclear Medicine Daniel Gillett [email protected]

Learning outcomes 

After this lecture you should be able to: – Explain what Nuclear Medicine is – Give examples of some clinical applications – Describe the differences between imaging techniques within Nuclear medicine i.e. static, dynamic and tomographic – Give examples of some limitations experienced in clinical practice

Lecture overview 

Introduction to Nuclear Medicine

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Planar imaging

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Dynamic imaging

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SPECT imaging

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PET imaging

Introduction

What is Nuclear Medicine? Use of unsealed radioactive sources Radionuclides are used to label pharmaceuticals These radiopharmaceuticals will usually mimic a physiological process The process can be used to diagnose diseases such as Parkinson's disease Can be used to treat diseases such as cancer

What is Nuclear Medicine? Diagnostic investigations Gamma and positron emitting nuclides such as Tc99m and F18 Imaging and sample counting

Nuclides used in Nuclear Medicine Nuclide

Half life

Use

C11

20 minutes

Co57

271 days

Sealed Source

Cr51

27.7 days

Sample Counting

F18

110 minutes

Ga67

3.26 days

Ga68

67 minutes

Ge68

271 days

I123

13.6 hours

NM Imaging

I125

60.1 days

Sample Counting

I131

8.02 days

Therapy

In111

2.81 days

NM Imaging

Kr81m

13 seconds

NM Imaging

Lu177

6.71 days

Therapy

Mo99

67 hours

Generator

O15

2 minutes

PET

Ra223

11.430

Rb81

4.6 hours

Generator

Se75

120 days

Sample Counting

Tc99m

6 hours

NM Imaging

Y90

2.67 days

PET

PET NM Imaging PET Sealed Source

Therapy

Therapy

Planar Imaging

Gamma Camera Overview  A gamma camera can give you a 2D image of the biodistribution of a radiopharmaceutical  Parallel hole collimator  Large NaI(Tl) crystal  Multiple PMTs  Position arithmetic circuits

Planar Imaging in Nuclear Medicine  Patient imaged with a static gamma camera  Radiopharmaceutical location fixed or changing very slowly  Typically takes several minutes to acquire enough counts for a clinically useful image  Typical matrix size 256 x 256 with a pixel size of ~ 2.5mm  Resolution ~ 6mm

Thyrotoxicosis  Imaging thyroid function is an example of planar imaging in Nuclear Medicine  The thyroid is an endocrine gland is the neck  It secretes hormones that regulate metabolism  An over active thyroid produces too many hormones and consequently an increase in the body's metabolism  This can cause symptoms such as: – Nervousness and anxiety – Hyperactive – a person can't stay still and is full of energy – Unexplained weight loss – Swelling of the thyroid called a Goitre

Thyroid uptake imaging  The thyroid uses Iodine to create the hormones it secretes  Sodium Pertechnetate is chemically very similar to Iodine  Therefore if you give a patient a known amount of radioactive sodium pertechnetate you can measure the uptake

Clinical protocol for thyroid uptake imaging  2.5% of annual workload  £230 per test  Low iodine diet for a week before investigation  Stop thyroid medication 4 days before investigation  75MBq of 99Tcm-Pertechnetate given intravenously  20 minutes uptake period  Patient positioned with thyroid in centre of field of view  2 minute image acquired. Patient is required to stay as still as possible  Uptake of the thyroid is calculated using a ROI on the image  From the ROI the activity in each lobe of thyroid can be determined

Thyroid uptake images

An overview of the kidneys  Another example of planar imaging is kidney function  The kidneys' primary function is to filter blood to remove waste, regulate the body's fluid balance and regulate the body's electrolytes  Kidneys are usually a similar size and contribute 50% to the function  Urinary tract infections can cause scarring in the kidneys and affect their function

How can we image the morphology and function of the kidneys?  Dimercaptosuccinic acid (DMSA) is a compound that can be labelled with 99Tcm  DMSA is treated like a waste product by the kidneys  During the clearing of DMSA from the blood it is trapped in the kidney  Therefore only the functional parts of the kidney have DMSA trapped in them  By imaging the distribution of 99Tcm you can visualise and quantify the functional parts of the kidneys

Clinical protocol for kidney morphology imaging  2.8% of annual workload  £270 per test  Patient administered with 75MBq of Tc99m-DMSA  3-4 hours uptake period  Patient positioned with their kidneys in the centre of the field of view  Anterior, posterior and lateral oblique images acquired  Each image is acquired for 5 minutes using a High Resolution Collimator  ROIs are drawn around the kidneys and the relative uptake can be determined  Consultant Nuclear Medicine Physician qualitatively assesses the images to find areas of reduced uptake i.e. non functional tissue

Kidney morphology images

Whole Body Planar Imaging  A typical gamma camera has a field of view of around 40cm x 50cm  This can limit the extent of image acquired  Often entire body images are required and therefore certain gamma cameras can acquire images while they move the patient in front of the detector  Just like a digital camera acquiring a panoramic image

Overview of bones  A standard adult human skeleton has 206 bones  Bones provide protection and structure to the body  Bones made up of a matrix that consists of calcium and phosphates  This matrix constantly being broken down and remade in a process called remodelling  This process is increased if there is damage to the bone  Bone damage can be caused by many things such as trauma and cancer

How can we image the bones?  There are a few phosphate compounds that can be labelled with 99Tcm  These include hydroxymethylene diphosphonate (HDP)  HDP is incorporated into the bone matrix as it is remade  The amount of HDP in the bone is proportional to the rate of remodelling  An image of the 99Tcm therefore shows the function of the bones  Areas where increased bone function is seen are often referred to as 'hot spots' because of their appearance on a bone scan

Clinical protocol for a bone scan  16% of annual workload  £250 per test  The bulk of most Nuclear Medicine department's workload will be whole body bone scans  550MBq of 99Tcm-HDP is administered intravenously  2-4 hours uptake time  During this time around 30% of the radiopharmaceutical is excreted via the kidneys therefore the patient must empty their bladder just before imaging  15cm/min gantry speed therefore whole body image acquired in around 20 minutes using a High Resolution collimator.  Images reviewed by doctor  Sensitive but not specific

Bone Scan

Dynamic Imaging

Dynamic Imaging  Many biological processes are rapid  Static planar imaging would not be useful  In these cases sequential images can be taken  Usually a more sensitive collimator is required to get the counts required for a good image  The rate of image acquisitions must be great enough to sample the process you are investigating

Filling the bladder  As previously mentioned the kidneys filter the blood and create urine  The urine that is created usually travels from the functional part of the kidney (cortex) through the collecting system (pelvis) and ureters to the bladder  This process can be affected by diseases such as hydronephrosis (stretched and swollen kidneys) and physical obstruction such as kidney stones

How can we image the bladder filling?  There are 2 pharmaceuticals that can be labelled with 99Tcm  These include mercaptoacetyltriglycine (MAG3) and diethylene triamine pentaacetic acid (DTPA)  Both compounds are treated like waste products and are excreted by the kidneys  This process happens straight away and the majority of these compounds are cleared within an hour of administration  Acquiring a dynamic image of this process is called a renogram

Clinical protocol of a renogram  5.6% of annual workload  £340 per test  The patient is required to be well hydrated and positioned with their kidneys in the centre of the field of view  They are administered with 75MBq of 99Tcm-MAG3  The images are started at the same time as the administration  A lower resolution but higher sensitivity collimator is used  90 x 20 seconds images are acquired  The patient must stay still throughout the entire process

Renogram Image Processing  The series of images is processed by drawing ROIs around the kidneys, background areas and blood pool area  The ROIs are applied to all the images  The kidney counts from the ROIs are corrected for background counts. The hope is that you are left with just counts resulting from the kidneys...

 Using the blood pool counts as the input function you can correct the kidney curves  A technique called Patlak-Rutland processing is used  The corrected curves can be used to find the true uptake rate of each kidney

Kidney Uptake



Time

Renogram Image Processing

Renogram – Patlak Rutland method Kidney ROI Counts = True Kidney Counts + Vascular Background

K  f1   Bdt  f 2 B Divide by the blood counts

Bdt K   f2    f1  B B Left with an equation of a straight line

Renogram

Overview of the heart  The heart pumps blood around the body  It can be split into halves  The right side pumps blood to the lungs to oxygenate blood  The left side pumps the oxygenated blood the rest of the body  Each side is made up of 2 chambers an atrium and a ventricle  Atria pump blood into the ventricles  Ventricles pump blood to the lungs or the body

The importance of the left ventricle  All of the chambers are important but the left ventricle output is especially important because it pumps blood to the entire body  Cardiac output is dependent on the heart rate and the stroke volume (the amount of blood pumped out of the left ventricle a single heart beat)  Therefore if the fraction of blood ejected of the left ventricle is reduced then the cardiac output is reduced  Some cancer treatments can reduced the left ventricle ejection fraction (LVEF)  LVEF is a crucial factor in patient care the patients receiving these treatments

How can we measure the LVEF?  Cardiac gating  Dynamic imaging with ECG input  Images split into sections matching the cardiac cycle  Hundreds of images are added together to create one cycle  The set of images can be used to visualise the heart in more detail

How can we measure the LVEF?  To measure the LVEF we image the patient's blood  This requires labelling the blood with 99Tcm  Red blood cells (RBC) make up around 50% of your blood volume  Using a compound called pyrophosphate (PYP) it is possible to label RBC with 99Tcm without removing them from the body

Clinical protocol for imaging the LVEF 2.2% of annual workload £270 per test The patient is administered with 750MBq Tc99m-Pertechnetate 20 minutes after they have been given PYP Images are acquired using a general purpose collimator (medium resolution and medium sensitivity) and cardiac gating (12-24 gates) The camera is positioned above the heart and tilted to maximise the separation of the chambers The total acquisition takes around 15-20 minutes Processing is performed on the gated image by positioning a ROI over the left ventricle

Images used for calculating LVEF

Calculating the LVEF

SPECT imaging

Overview of SPECT imaging  Typically 60 – 120 projections are acquired  Usually with a pixel size of 4-5mm  A high resolution collimator is used  A reconstructed image has has poorer resolution than planar imaging but improved contrast  In our department we exclusively use iterative reconstruction

Overview of filtered back projection  Fourier transform (FT) of the projection data  FT of the projection data is modified (filtered) to take account of the sampling problem  Inverse FT of the modified data is taken  These modified projections are backprojected  The filter required is a ramp in frequency space

Overview of iterative reconstruction  Make a guess at the image – FBP often used  Forward project to determine data  Compare with measured data – Cost Function  Modify the guess  Continue until consistent with data

Overview of neurotransmitters  Information is transmitted through the body using cells called neurons  Neurons make a chain and pass electrical signals along this chain  Signals are passed from one neuron to another across a gap called a synapse  Neurotransmitters carry the electrical signal across the synapse  Dopamine is a type of neurotransmitter

Overview of Parkinson's disease (PD)  The caudate nucleus and putamin are parts of the brain that are responsible for body movements  PD is a degenerative disease which affects neurons in this part of the brain  These neurons have a high concentration of dopamine transporters  As the number of neurons in this part of the brain reduce the patient begins to develop the symptoms of PD such as a tremor and difficulty with movements  These symptoms can also be caused by medication but only in PD will there be a reduced number of dopamine transporters

How can we image dopamine transporters  Cocaine analogues have a high affinity for dopamine transporters  Ioflupane is a cocaine analogue that can be labelled with (DaTSCAN) – There are no cocaine analogues that can be labelled with 99Tcm

 Ioflupane binds to the dopamine transporters  Patients with PD have reduced uptake  Patients with PD symptoms caused by medication have normal uptake

123

I

Clinical protocol for DaTSCAN  1.5% of annual workload  £1250 per test  185MBq of 123I-Ioflupane administered intravenously  3 – 6 hours uptake period  The patient is positioned with their brain in the field of view – However for the best images the shoulders should out of the way of the rotating camera

 120 projections (acquired by 2 detectors), 30 seconds each  The patient is required to stay still through out the acquisition – This is especially difficult for these patients

DaTSCAN results

DaTSCAN results

Post ablation thyroid imaging Patient receiving 131I-NaI for thyroid ablation are required to have imaging performed to visualise the extent and location of the remnant gland This is possible by using SPECT but due to the small structures in the neck it is very difficult to confidently know whether there is uptake in the thyroid bed or in an adjacent lymph node An additional CT is done to provide anatomical information

Post ablation thyroid imaging The patient receives between 1100 and 5500MBq of I131-NaI for ablation of the remnant thyroid post surgery 1 to 4 days post treatment the patient is imaged 120 projections (acquired by 2 detectors), 15 seconds each Low dose CT scan acquired without the patient moving The reconstructed SPECT images can be viewed overlaid onto the CT images

Post ablation thyroid imaging

PET/CT Imaging

Overview of glucose and how to image it  Glucose is a sugar  Sugars are used to fuel many biological processes  These processes include mitosis (cell division), muscle contractions (including the heart) and heat production from brown fat  Cancer cells require a lot of energy due to their rapid cell division  A glucose analogue called Fluorodeoxyglucose (FDG) can be made with radioactive 18F  Imaging the distribution of 18F highlights areas of high glucose use

Clinical protocol for FDG  8% of annual workload  £360 per test  The patient receives 370MBq of 18F-FDG  During their 60 – 90 minute uptake period the patient is isolated and asked to relax  The patient is imaged in sections called bed positions  Each bed position is around 40cm and lasts approximately 3 minutes  A CT is acquired covering the same area as the PET, this is used to correct for attenuation and is required for quantification (SUV)

FDG images

Pituitary adenoma  0.4% of annual workload  £500 per test

 The patient receives 370MBq of 11C-Methionine  20 minute uptake period  Methionine is taken up anywhere protein's are synthesised  One bed position for 20 minutes  An adenoma will have more uptake than the regular pituitary  The images are reviewed by a doctor and the result is often used to guide surgery

Pituitary adenoma

PET/CT Gating  PET/CT data can be gated using respiratory data  This requires the collection of the data to be split up into phases of the respiratory cycle  Performed using a camera and a reflective marker on the patient's chest  Corresponding CT data is required for matched attenuation correction and for localisation

PET/CT Gating

PET/MR  The future...