Module 2.1: Imaging modalities

Question 1

MRI Disadvantages

Answer 1

• Ferromagnetic artefact from unsuitable material
o Stainless steel/titanium objects which won’t be moved but will damage the image
o If magnetic  will attract to the centre of the bore  fatality (oxygen cylinders)

• Pacemakers can’t be scanned
o There are new MR compatible types but they still need to be switched off during scanning

• Calcification hard to visualise, as there is not enough concentration of free protons

• Patient comfort:
o Claustrophobia
o Long time
o Noisy

Question 2

Advantages of MRI

Answer 2

• No ionising radiation
o No longer acceptable to use consistently high doses in diagnostic imaging
o CT equivalent is 400 CXR for one body part
o It is common to do 3 parts – 1200 CXR

• Multiplanar
o You can image in any plane without moving the patient
o These are direct scans and not reconstructions
o Only USS can approach this type of facility, but that has other limitations

•	Exquisite soft tissue resolution (area of abnormality can be easily identified by manipulating the following:)
o	Water content 
o	Contrast transit 
o	Flow 
o	Mineral and crystal content
o	Phase 
o	Perfusion and diffusion
o	Heat sensitivity 
•	Many new contrasts (alteration of protein relaxation factors)

Question 3

T1 vs T2 MRI

Answer 3

T1
Longitudinal vector
Spin-lattice interaction
Large signal, good anatomy
Low water signal 
Short echo time and relaxation time

T2
Horizontal vector
Spin-spin interaction 
Smaller signal, more sensitive to pathology
High water signal
Long echo time and relaxation time

Question 4

MRI Applications in the brain

Answer 4

water content i.e. CSF is dark in T1 but bright in T2

Can also see small structures such as nerves (bottom left) –> facial and vestibulocochlear nerves seen

Can also visualise vessels without using contrast  circle of Willis

Question 5

Diffusion Imaging in MRI

Answer 5

Measures movement of water  movement of water is restricted by cell packing, hence in cancers where this occurs, one can visualise tumour due to diffusion restriction

In brain, this allows for rapid imaging of ischaemia within 30 minutes of onset as net decrease in diffusion will correspond to areas of ischaemia

*** If an infarct is seen in T2, a diffusion MRI can be used to differentiate new and old lesions

Question 6

Functional Imaging in MRI

Answer 6

• Utilises O2 sensitive images in the brain (as blood supply increased to active areas)
• Widely used in psychiatry and tumour resection to avoid resecting areas surrounding tumour which may have been moved during growth

Question 7

joint imaging in MRI

Answer 7

• T1 weighted imaging showing all soft tissue structures including fat near patella tendon
• High resolution imaging of articular cartilage can also be taken  has a trilaminar appearance
• Can also visualise ligaments e.g. in elbow, which appear as low-signal intensity
• Can also visualise osteochondral lesions e.g. infarcts and neuromas (hypertrophy of

Question 8

MR angiograms

Answer 8

• Use IV bolus Gd contrast to shorten T1 and produce v bright blood
o Rapid bolus gd at 2mls/sec

• Background is suppressed or subtracted
• Timing is critical
• Excellent visualisation of arterial tree with few artefacts
• 3D Fourier transform to acquire data

•	Advantages
o	No ionising radiation 
o	No nephrotocic agents
o	Small volume contrast 
o	High sensitivity and specificity compared to IADSA (inter-arterial digital subtraction angiography
o	All in one breath hold

• Can show pathology: aortic aneurysms, arterial stenosis, as well as integrity of renal transplants e.g. stenosis of renal arteries in transplant, extent of peripheral disease can also be assessed (renal failure and claudication)
• Cardiac MR is now also a very specialist area

Question 9

Uses of MRCP

Answer 9

MRI of the biliary tree

o T2- weighted area that makes the fluid very hyper-intense (bile) where one can view: gall bladder, common bile duct and intrahepatic ducts as well as pancreatic duct
o Filling defects means that stones are found  can visualise number and shape, as well as any dilation of the tubes (upper right)
o Malignancies can also be detected via obstructions (lower right  ampullary malignancy)

Question 10

Liver Specific Contrasting Agents in MRI

Answer 10

RES (reticuloendothelial – Kupffer cell) agents
• Iron particles blacken liver with normal RES – lesions appear bright
• Reveals 27% more lesion than unenhanced MRI
• 40% more lesion than contrast CT (Ros & Freeny Radiology)

Hepatobiliary agents
•	Actively taken up by hepatocytes and cause increase in signal
•	MnDpDp Hamm 
o	390 liver lesions, 272 with T2 MRI
o	Gd BOPTA (multihance) similar

Question 11

MRI in imaging of adrenals

Answer 11

adrenal myelolipoma on a T1-weighted image
o Can tell from high fat content
o Large mass in right adrenal
o Hyper-intense
• Can also complete fat saturation and confirm fatty nature

Question 12

MRI imaging of the cervix

Answer 12

MRI is useful to visualise organs of pelvis and contents of those organs (see right)

o Can also visualise how the endometrial cavity changes throughout menstrual cycle (distension of endometrial cavity seen during menstruation)

o Can also visualise abnormalities such as: bicornuate uterus (two endometrial cavities spread apart with a common cervix) and uterus didelphys (2 myometriums, vaginas and often cervices), cervical and endometrial tumours –> can use MRI to stage tumours

Question 13

uses of MRgFUS

Answer 13

(Magnetic Resonance guided Focused Ultrasound Surgery)

• Totally non-invasive  reduced trauma
• Real time, diagnostic imaging based, decision support  improved quality and efficacy
• Real time monitoring and control of the therapeutic process
• Outpatient treatment  no or minimal required hospitalisation
• Significantly reduced recuperation time
• No side effects – repetitive treatment possible

Question 14

Why diagnose fibrosis?

Answer 14

• To diagnose cirrhosis  initiate surveillance for complications: HCC and oesophageal varix
o Surveillance starts when patients are diagnosed with cirrhosis

• To prioritise/assign treatment
o If there is no advanced fibrosis in Hep C, defer treatment until IFN-free

• To motivate/reassure patient
• To provide prognostic information
• To develop new technologies/therapies

Question 15

Staging of fibrosis

Answer 15

• ISHAK (o-6) scoring system

•	METAVIR (0-4) scoring system
o	Enlarged portal tract but no septa (fibrous strands)
o	Enlarged portal tract with few septa
o	Numerous septa
o	Cirrhosis

Question 16

Strengths and limitations of biopsies to diagnose fibrosis

Answer 16

Deemed to be the Best Available Gold-Standard

Strengths
• Provides information on inflammation (necro-inflammation or grading), steatosis, infiltration/granuloma and other pathological finding
• Diagnostic features may be seen and specific stains applied

Limitations – Standish et al, Gut 2006
• Sampling variability – only small sample is created from biopsy
• Intra and inter-observer variation
• 2D view
• Semi-quantitative categorical approximation of continuous process

Expensive, time-consuming, lots of staff needed, discomfort to patient.

Question 17

Accuracy of biopsies to diagnose fibrosis

Answer 17

• Correct prediction of fibrosis stage or cirrhosis in 80% of cases
o Based on post-mortem studies (Afdhal N. Hepatology 2003)

• Accuracy increases with increasing length
o Correct prediction of fibrosis stage 65% at 15mm, 75% at 25mm (Bedossa P et al. Hepatology 2003)

• Inter-observer variability
o 10% of biopsies assessed as differing fibrosis stage between 2 histapathologists (Regev et al. Am J Gastroenterol 2002)

Question 18

Complications in biopsies to diagnose fibrosis

Answer 18

• Minor – 3-30%
o Local pain, haematoma

• Major – 0.3-0.6%
o Perforation of a viscus, pneumothorax, major intraperitoneal haemorrhage, sepsis

• Death – 0-0.03%

Question 19

Summarise the alternatives to biopsies to diagnose fibrosis

Answer 19

Non-invasive Markers
• Indirect
• Direct

Imaging biomarkers
• Ultrasound based (including transient elastography)
o Fibroscan  only one currently validated for use in clinical practice
• Magnetic resonance
• CT

Question 20

Describe the procedure of Fibroscan to diagnose fibrosis

Answer 20

Transient Elastography
• Ziol M et al, Hepatology, 2005:

o USS transducer mounted along axis of a pulsing tip (vibrator) –> vibration is of mild amplitude and low frequency (50Hz) inducing an elastic shear wave

o Shear wave (pulse) propagates/travels through the liver

o Pulse echo ultrasound device follow the propagation of the shear wave and measures its velocity

o Velocity related to elasticity of the liver  the higher the velocity the greater the fibrosis

o Stiffness measured in kPa
Range: 1.5-75kPa
Normal: 1.5-7.5 kPa

Question 21

Describe the technique of fibroscan

Answer 21

• Patient lies in dorsal decubitus position with R arm in maximal abduction
• Operator locates probe to liver portion >6cm thick and free of vascular structures/gallbladder
• Right lobe liver – through intercostal spaces
• Takes <10 minutes, generally well-tolerated
• To be valid, intrinsic variability must be <30% (low variability between samples) and success rate must be >60%
• Requires ten valid measures
• Success rate = number of valid measures/number of total measures
• Result: median of the ten valid measures (kPa, range 2.5-7.5)
• CAP Score (C-attenuated parameter) – is a measure that indicates amount of fat present in liver (<225 is normal)
o Based on the properties of ultrasonic signals acquired by TE
 Fat affects ultrasound propagation
 Use TE acquired measurements , ie internal validation
o Rapidly, painless with high patient acceptance; score 100-400
o Can accurately grade the severity of steatosis in patients with CLDs

Question 22

pros and cons of fibroscan

Answer 22

Pros	
•	Simple training
•	Sampling greater portion of liver tissue compared with biopsy
•	Reliable measurement
•	Real time assessment
•	Completely non-invasive
•	Quick (circa 5mins)
•	Evidence based support
•	Applied in many settings (CHC, CHB, HCV/HIV, PBC/PSC, portal hypertension, acute inflammation)

Cons
• Can’t probe in narrow IC spaces as can’t get probe close enough to liver
• Effect of cholestasis/congestion, fat, ascites, oedema/inflammation, portal HTN
• Ethnicity/age/food (TE measure increases 25% after meal, requires standardisation)
• Expensive kit
• Different ranges in different populations (need to standardise measurements)
• Experts required to interpret results
• Obese/waist circumference  overestimate liver stiffness
• Sometimes not possible (~20%)  failure to get result in 5% and failure to get reliable result in 15% (IQR/success rate)
• What does liver stiffness really mean? (serves as a surrogate marker of fibrosis)

Question 23

Summarise the new developments in fibroscan

Answer 23

• XL probe
o Differs from M probe
o Uses lower frequency
o More sensitive transducer
o Deeper focal length
o Larger vibration amplitude
o Greater depth of measurement beneath skin surface
o Elkashab et al, Hepatology, 2012: 276 patients with NAFLD and viral Hep (BMI>28kg/m2) tested with both skin biopsy and TE with both probes. Showed that TE is useful in both
 XL probe: lower median stiffness measures hence needs lower cut-offs

• Correlates with HVPG (hepatic venous pressure gradient  measure of portal hypertension)
o Bosch, J Hepatol, 2011: TE £21.1kPa – 100% negative predictive value for occurrence of portal HT complications
o ALD – higher kPA than viral hepatitis for same HVPG

• Spleen Stiffness
o Spleen plus liver stiffness predicts liver disease severity
o Colecchia et al Gastro 2012: spleen stiffness predicts HVPG

Question 24

Advantages of serum biomarkers to measure fibrosis

Answer 24

good repreducibility

widely available

no cost

well validated

can be done as an outpatient

Question 25

disadvantages of serum biomarkers to measure fibrosis

Answer 25

non-specific

unable to discriminate between the stages

Question 26

Interpretation of NMR

Answer 26

• Atoms with an odd atomic number are considered to be MR responsive, and so will give off a signal
• In human MRI scanners, hydrogen/proton scanners are used as water (majority of our body) consists of H1 atoms  molecules will therefore spin to give off a signal
• In chemical fluids/components used in MR Spectroscopy, different consitituent molecules will spin and give off a different radiofrequency spectrum thereby producing a ‘chemical shift’ and peaks that can be seen for each molecule

• Each atom has its unique chemical frequency and this is determined by peak position, which itself is determined by the local chemical environment

o E.g. a phosphorous atom in ATP will be a different frequency to that of a phosphorous atom in a phospholipid
o The more of the molecule present, the higher the peak

Question 27

Nuclear Spin of different atoms

Answer 27

• Zero spin: no effect in an applied magnetic field, for example: 12C, 32S
• Dipolar: spin ½ - narrow linewidths, for example: 1H, 13C, 19F, 31P
• Quadrupolar: spin > ½ - efficient relaxation so very broad lines: 33S, 67Zn

Question 28

Limitations of Patient Handling in MRS

Answer 28

• Requires an hour
• Metal check
• Claustrophobia
• Restriction of patient size

• Safety:
o NRBP guidelines for static magnetic field, time dependent magnetic field and radiofrequency
o Metal check for all personnel
o Controlled environment – restrictions for subjects with metal implants and no loose metal objects

Question 29

Why study the liver:

Answer 29

o Principal homeostatic organ in the body
o Responsible for metabolism of fats, carbohydrates, circulating proteins and the detoxification of the body’s waste products
o Most important site for drug metabolism
o Bile is produced in the liver
o Largest organ in the body which has a convenient anatomical location for MRS

Question 30

Uses of NMR in the liver

Answer 30

o Assessment of energetics (NTP - ATP, Pi)
o Assessment of membrane turnover (PME – phosphomonoesters i.e. precursor to membranes, PDE – phosphodiester i.e. degradation product of membrane, Cho - cholene)
o Assessment of glycogen and lipid metabolism (13C, 1H MRS)
o Levels of endoplasmic reticulum (PDE)
o Glycolytic/gluconeogenic intermediates (PME)
o Metabolites of fluorinated drugs (19F MRS)

Question 31

Clinical Research Applications in GI

Answer 31

• Functional capacity of the cirrhotic liver
• Grading of liver disease in hepatitis C
• Markers of allograft rejection
• Dynamic assessment of donor liver viability
• Characterisation of tissue in Barrett’s oesophagus
• Biomarkers of cholangiocarcinoma in bile

Question 32

Assesing the Functional capacity of the cirrhotic liver via MRS

Answer 32

Taylor-Robinson et al, Liver 1997

o Decompensated cirrhotics in vivo have lower PDE (degradation products) levels and higher PME

o This indicates that lower levels of energy metabolism so PME/PDE ratio is a sensitive marker for cirrhosis, with potential to differentiate cirrhotic severity

o Changes in PME/PDE can be interpreted as the failing liver attempting to regenerate
 Normal regeneration = 4x in a 70-year-life span, cirrhotic regeneration = 4x a week/day (hence scope for DNA mismatch)

 Sensitive marker for cirrhosis
 Potential for differentiating severity of disease

Question 33

Grading of liver disease in hepatitis C via MRS

Answer 33

o PME/PDE ratio can be used to measure severity of fibrosis – Lim et al, Hepatology 2003

 PME:PDE of over 0.3 had 82% sensitivity and 81% specificity for cirrhosis
 Specificity for differentiating mild hepatitis from severe disease = 83%

 Potential for differentiating severity of disease using PME/PDE
 Ability to differentiate mild hepatitis, moderate hepatitis and cirrhosis has therapeutic implications

Question 34

Markers of allograft rejection via MRS

Answer 34

o Chronic ductopenic rejection involves chronic loss of interlobular and septal bile ducts which begins 6 weeks to 6 months after transplantation and is PATCHY, hence poorly reported using liver biopsy, though a reliable early diagnosis is essential

o PME/NDP and PDE/NDP ratios are raised in rejection

o Due to altered membrane phospholipid metabolism and contribution from altered bile phospholipids

Question 35

Dynamic assessment of donor liver viability via MRS

Answer 35

o MRS can be used to develop better preservation fluids and storage methods, and allow testing of marginal donor livers to confirm their viability by simulation i.e. reperfusion of the liver in vitro
o Changani et al, Transplantation, 1999:

 During reperfusion of isolated livers, 31-P is used to study the success of ATP generation which will confirm liver viability

 Use MRS to look at ATP levels

Question 36

Characterisation of tissue in Barrett’s oesophagus via MRS

Answer 36

o In vivo/in vitro 31P MRS of normal liver
o High-resolution MRS from a semi-solid sample
 NMR theory: many of the local interactions have an orientation dependence determined by (3cos2theta-1)
• Theta is the angle between the interaction vector and the applied magnetic field (54.7 degrees angle)
 NMR answer: physically spin the sample at theta so these interactions go to zero
• Theta is so called the magic angle
o Summary: if you spin a solid sample at a 54.7degree angle in a magnet, the solid sample behaves as a liquid would

o The Warburg hypothesis
 Cancer cells have an altered energy metabolism, lacking glycolysis
 Carcinogenesis: alterations in cell cycle control, deregulated proliferation, escape from apoptosis and cell immortalisation
 Summary: more anaerobic glycolysis in tumour cells

o Warburg hypothesis can be applied to NMR Spectroscopy
 31P MRS of extracted tissue predicts tumour stage and lymphatic invasion in oesophageal cancer – Merchant et al, Biomed, 1999
 Increased choline levels observed subsequent to malignant transformation in human prostatic epithelial cells – Ackerstaff et al, Cancer Res, 2001

 Significant differences in Cho/Cr and lipid-CH3/Cr ratios between squamous and columnar epithelium
 Histology is preserved after MRS (better in squamous than columnar)

Question 37

Biomarkers of cholangiocarcinoma in bile via MRS

Answer 37

o MRS may be used to do metabolic profiling of bile (provide biomarkers of disease in CCA enabling improvements in diagnosis and treatment of bile) to see if people are at risk of cholangiocarcinoma
o Hypothesis
 Total bile acids are raised and phosphatidylcholine (PtC) reduced in bile in CC
o Aim
 To use in vitro MRS to quantify bile acids and PtC in CC bile and suitable controls
o Both 1-H and 31-P NMR spectra showed phosphatidylcholine to be reduced in CC bile – Khan et al, Eur J Gastroenterol Hepatol, 2005

Question 38

Summarise the importance of MRI Endoscopy in CC

Answer 38

PSC difficult to distinguish bw CC

CC
• Tricky to characterise, particularly in patients with pre-existing benign biliary disease
• Diagnosis based on blood markers, radiology, endoscopy, surgery and histology

only 50% of perihilar tumours have laparotomy and are considered suitable for surgery

• Resection possible in under 1/3 cases

5y survival
 19-47% (clear margins)
 0-12% (positive margins)

Question 39

classification of CC

Answer 39

Bismuth staging

o Staging not good at predicting resectability or survival –Zervos et al

Question 40

BSG guidelines on diagnosis of CC

Answer 40

– Khan et al, 2002 and 2009

- Clinical Features
Jaundice
Pale Stools
Dark Urine
Pruritis
Malaise
Fatigue
Loss of Appetite
Weight Loss

- Serology
Bilirubin
ALP
GGT
ALT/AST

• Tumour Markers
  CA19-9
  CEA
  CA-125

- Radiology
USS
Contrast-enhanced triple phase helical CT
Or Helical CT
MRI
MRCP
PET

- Invasive Investigations
(ERCP)
PTC
EUS
Histology

Question 41

ERCP in CC diagnosis

Answer 41

• Uses a side-viewing duodenoscope, a bridge permits angulation of the catheter
• Allows injection of contrast, stent insertion/removal, stone removal, cell sampling
• Limitations include: complication rate, limitation to 2D view, lack of extra-ductal information

Question 42

Cytology in CC diagnosis

Answer 42

• Current diagnostic gold standard at endoscopy

* Very low sensitivity even in expert hands

Question 43

MRI in CC diagnosis

Answer 43

• Can acquire clinical images and study tissue metabolism in vivo
• Operation based on difference in energy of nuclear spin states in magnetic field
o Proton 1H has spin ½ and 2 possible states
o Energy difference DE = hf = ghB/2p
o For 1H, g/2p = 42.57 MHz/T so RF frequency
o Value of g sensitive to proton environment, allowing tissue contrast differentiation
• Resonance = exchange of energy between two systems at the same frequency
• Resonance frequency is proportionate to B0

Question 44

Advantages and Limitations of MRI and MRCP

Answer 44

• Powerful magnet, transmitter coil and receiver coil integrated into scanner gantry
• Resolution good but measured in millimetres
• Resolution degraded further when images composited in MRCP
• Safe
• No tissue diagnosis or therapeutic function
• Signal degraded by distance from receiver coil (1/r3) and motion artefact
o A receiver coil apposed directly to the tissue should allow better resolution (what MRI endoscopy is)
o Compensation for movement artefact would also enhance resolution

Question 45

MRI endoscopy projct aims

Answer 45

• Engineering and Physical Sciences Research Council (EPSRC) grant to develop a micro-engineered MR receiver coil with sub-millimetre resolution
• Integrate it into a MR compatible biliary catheter
• Integrate tissue sampling capability
• Build an MR compatible duodenoscope
• Develop a system to compensate for respiratory artefact
• Produce ex vivo high resolution biliary images
• Develop plans for a translational clinical study

Currently, biliary coil, field modifier and non-magnetic duodenoscope have been develop and tested in ex vivo animals and humans. Currently it is under in vivo volunteer trials in Thailand.

Question 46

Microcoil Requirements in MR endoscopy

Answer 46

• Microcoil must be:
o Cheap, single use, sterilisible, MR-compatible, watertight, electronically safe, flexible (to make turn)
o System must allow tunability, allow access to catheter lumen, allow identification of device position by including fiducial material
o Useable through 3.2mm channel in endoscope, with deflection over bridge

• Operation of RF detector coils
o Use L-C resonator  performance determined by quality factor
o Require capacitors for matching and tuning, but these are bulky and hard to integrate

• State of the art in microcoils
o Many catheters as one off wire-wound coils
o Some flexible planar microdevices, few catheterised
o Ahmed et al, Micromech. Microeng, 2009
 Prototype microcoil biliary catheter developed, in which microcoils are integrated into a conventional cytology brush
 Coil is made flexible by being made of Cu electroplated polyimide
 Good electrical performance
 Tunable for H MRI at 1.5T and 3T (other nuclei possible)
 Excellent resolution: submillimetre with use of ‘phantoms’
 Uniform sensitivity along 60mm coil length
 Biliary imaging performed using ex-vivo porcine liver tissue
 Sub-millimetre resolution obtained over large FOV

Question 47

Field Modifier

Answer 47

• Generates own 1 mT field
• Can shift scanner magnetic field up to 50mm in each plane
• Currently activated with abdominal sensor
• Plan to combine with tracking of probe or liver

Question 48

Non-Magnetic Duodenoscope

Answer 48

MR compatible (non-magnetic duodenoscope) has been developed:
o Uses fibre optics viewed through an eyepiece
o Suction, insufflation and light source available through ultra-long umbilicus
o Metal parts in titanium and phosphor-bronze

• Duodenoscope tip receiver coil developed

Question 49

Basics of PET (Positron Emission Tomography)

Answer 49

• Inject proton-rich radioligand (a compound that is a substrate for a physiological process)
o FDG-PET is the most commonly used ligand  fluorine radiolabelled glucose
• Positrons exit nucleus & collide with free electrons  total annihilation
• Photons detected by detectors

Question 50

hallmarks of cancer that can (theoretically) be imaged using PET scanning

Answer 50

o	Sustained proliferative signalling (most frequently imaged)
o	Evading growth suppressors
o	Activating invasion and metastasis
o	Enabling replicative immortality 
o	Inducing angiogenesis
o	Resisting cell death

Question 51

Explain the Warburg effect

Answer 51

• Malignant tissues utilise more glucose, as it is associated with increased glycolysis
• If sugar is attached to a radioactive tracer in a bond, it will be taken up by cancer cells
o Deoxyglucose is labelled with fluorine-18 to become fludeoxyglucose (FDG)
• Upon entering the cancer cell, glucose changes to G-6-phosphate and undergoes no further change (trapped) and can be imaged with a suitable camera
• FDG uptake is a marker of cell proliferation, aggressive behaviour and grading, particularly in lymphoma, lung, brain and soft tissue cancers amongst others

Question 52

Recommended Applications in Oncology of PET

Answer 52

• Benign Vs malignant masses (lung nodules)
o Lung carcinoma - In differentiating benign from malignant solitary pulmonary nodule, FDG is diagnostic in 94% of cases while trans-thoracic needle aspiration in 66% of lesions (Dewan et al chest 1995)
• Establishing grade of malignancy (brain tumours)
• Localization for biopsy purposes (head and neck)
• Treatment planning (brain, lymphoma)
• Establishing local and distant extent of tumour
• Monitoring therapy effect
• Assessment of recurrences and their staging
• Identifying primary of unknown origin

Question 53

PET in Non-Small Cell Lung Cancer

Answer 53

• NPV of 95% for primary lesion
• Detection of metastasis not picked by CT
• Assessing adrenal masses seen on staging CT (sensitivity 100% specificity 80%)
• Detection of recurrence
• Assessing response to treatment

Question 54

PET in GI tumours

Answer 54

• Oesophageal Carcinoma
o Diagnostic with sensitivity 80%, specificity 95%
o Clinically important in detecting distant metastasis

• Hepatocellular Carcinoma
o Sensitivity less than CT (55% vs. 90%)
o Uptake proportional to differentiation and grade
o Picks up metastasis not picked up by CT – Khan, J Hepatol, 2009

• Colorectal Cancer
o Pre-operative detection of metastasis [MAIN ROLE OF PET IN CRC]
 Valk et al, Arch Surg, 1999 – prospective blinded study comparing PET with CT in 155 patients with recurrent colorectal cancer. PET compared to CT had greater sensitivity (93% vd. 69%) and specificity (98% vs 96%). PET showed additional sites in 29% of cases. Potential savings at $3000 per patient.
o Sensitive but not specific in primary tumour
o Early detection of recurrence
o Assessment of high CEA & negative CT
o Assessing therapeutic response

Question 55

PET in Lymphoma

Answer 55

• FDG has very high avidity for lymphoma
• Uptake correlates with proliferative activity
o Pre-therapy high uptake = poor prognosis
• PET Vs CT: Sensitivity 86% vs. 81%; Specificity 96% vs. 41%
• Detects additional sites unsuspected by CT
• Influences staging in up to 16% of patients

Question 56

Imaging αvβ3 in PET

Answer 56

• αvβ3 is an integrins are cell adhesion molecules
o Interact with ECM via Arg-Gly-Asp (RGD) peptide ligands
o Integrin αvβ3 up-regulated on tumour endothelial cells

• Radiolabel peptides to image αvβ3 levels
• Fluciclatide, a radiolabel peptide to image αvβ3 – Sharma JNM 2015

• 3’-deoxy-3’-[18F]-fluorothymidine (FLT) is a new marker of proliferation (remember thymidine is a building block of DNA) – early response biomarker particularly to cytotoxic chemotherapy (can tell early on whether patient is going to fare well from chemotherapy)

Question 57

Somatostatin Receptor Imaging

Answer 57

• There are 5 subtypes of somatostatin receptor (1-5)
o 70-90% SSTR 2 & 5
• Somatostatin analogues bind with high affinity to SSTR2 & 5
• Use radiolabel analogue with gallium for PET imaging
• This can be used for staging (measure how far neuroendocrine tumour has spread)
• Peptide receptor radiotherapy or theranostics

o Indium, yttrium, lutetium labelled somatostatin analogues (i.e. long-acting somatostatin analogues instead of gallium which is short-acting)
o These receptors internalise the somatostatin analogue and this can be used to deliver high dose radiotherapy (hence it would be a more targeted therapy for cancer in these patients)