Medical imaging modalities: comparison. Functional imaging.

Nuclear Medicine: aims, principles.

Univ. of Debrecen Department of Nuclear Medicine

2010 02

22

Nuclear Medicine: Manuals

• Link to English reference manual:

http://www.auntminnie.com/index.asp?sec=ref&sub=ncm

• Lectures in English:

http://www.nmc.dote.hu/nmt_eng/oktatas_e.htm

• In Hungarian:

http://www.nmc.dote.hu/nmtk/index.html

• Book: A Nukleáris Medicina Tankönyve(Szerk. Szilvási I.; B+V Kiadó, 2002, 2010)

• Required reading:Taylor A., Alazraki N., and Schuster D.M.:A Clinician's Guide to Nuclear Medicine (2nd Edition)

The Society of Nuclear Medicine, Reston, 2006ISBN: 0972647872

3

The clinical diagnostical possibilities in recent years:

Patient history!!!

Physical exam. (Palp., auscultation etc).!!! No idea???

Sampels Functional map’s Struktural analisis

(Chem.Lab) (Nuklear medicine: (Radiology)

molekular map )

Biochemical, Kamera, SPECT, PET Rtg, UH CT, MR

microbiological

data

„Multimodality”

methodes SPECT-CT PET-CT PET-MR?

44

Source: „What is Nuclear Medicine?” (SNM)

Medical imaging, Historical paralells:

Surgery Internal med. Oncology

Medical imaging, Historical paralells:

Surgery Internal med. Oncology

55

Targets and tools of medical

imaging

6

First inventions: spontaneous

radioactivity ...

ANTOINE HENRI BECQUEREL(1852-1908)

1903 Nobel Laureate in Physics

„in recognition of the extraordinary

services he has rendered by his

discovery of spontaneous

radioactivity”

MARIE CURIE (1867-1934)

PIERRE CURIE (1859-1906)

1903 Nobel Laureates in Physics

„in recognition of the extraordinary

services they have rendered by their joint

researches on the radiation phenomena

discovered by Professor Henri Becquerel”

7

The beginnings of NUCLEAR

MEDICINE: a Nobel priced idea

1924: Principle of radiotracer

applications:

Changing an atom in a molecule for its radioisotope

will not change its chemical

and biological behaviour significantly.

Consequence: the movement,

distribution, concentration of the

molecule can be measured with

radiation detectors.

György HEVESY (1885-1966)

1943 Nobel Laureate in

Chemistry„for his work on the use of

isotopes as tracers in the study

of chemical processes” 88

Selecting the radionuclide for imaging

C-11

N-13

O-15

F-18

e-

γγγγX-ray

Characteristic X-ray(following K-capture)

For external detection: electromagnetic radiation can be used!The main 2 groups of isotopes in nucl. Med.:

Gamma emittersgamma energy: 80-400 keV(if lower: attenuated inside the patientif higher: low detection sensitivity)

Positron emittersannihilation radiation:

2 ⋅ 511 keV

9

Most common radionuclidesin Nuclear Medicine

NuclideEnergy

(keV)Half time Used for: Note

Tc-99m 141 6.03 h many generator

Tl-201 68-80 73.1 h myocardium cyclotron

I-131 364 8 days thyroid +therapy

I-123 159 13 h thyroid cyclotron

proteins,...

I-125 27-35 60 days in vitro!

F-18 Beta+ 110 min PET!

10

Differencies between radiology and Nuclear medicine( only some exampels )

Radiology: (relatively closed)

Applied phyisics

First : instrument

Summ.X Ray, CT, MRI, US

Second: contrast. Mat.

Main Informations:

Structural, Anatomycal

Hybrid technics: CT +

(Common problem:

Nuclear medicine (opened disc.)

Applied molecular biology

First: radiopharmaceutical(FUNCTION, ORGAN OR TISSUE SELCTION)

Second: instrument Planar, SPECT, and PET cameras

Main info: functional,metabolic.

SPECT, PET

radiation burden )

11

Effective doses (mSv)

0

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Scintigraphy

Complicated radiological

Simple X-ray

12

Why Nucl. Med. is „opened” discipline?

example: Imaging brain receptors:PET ligands for imaging various receptor systems –MR structur is same!!

[F-18]-memantin(NMDA-receptor)

[F-18] fluoro-2-deoxy-glucose

O

OH

F

HO

OH

HO

N

SCH3NH2

FH2C

CH3

Cl

OH

Cl

OCH3

NHN

O CH2CH3

N

N

N

F

O

OCH2CH3

O

CH3

NH3C

H

H Cl

NO

Ph

[C-11]-raclopride(dopamine D2

receptor)

[C-11]-McN 5652(serotonin

transporter)

[C-11]-b-CPPIT(dopamine

transporter)

[C-11]-flumazenil(benzodiazepine-

receptor)

Source: G. von Schulthess, University Hospital, Zürich

1313

Medical & biological applications of radionuclides

the main fields of Nuclear Medicine

Medical applications

(nuclear medicine)

Research applications

(nuclear medicine)

Diagnostics

Therapy

„In vivo”

imaging

„In vitro”

Application of diagnostic

methods for research

„Molecular imaging”

Combination of analitical

laboratory methods with

radiotracer technique

„In vivo”

non-imaging

14

The Structure of full Nuclear Medicine workplace (in 2009)

PET

PlanarSPECT

CT

Trans

lationLiquidPET-CT

Cell

labell

Fluoro

Pain

killing

Synovior

thesis

Immuno

Zevalin

I.In vivo II.In vitro III.Therapy

RIAHigh dos

Jodine

15

Thyroid scintigraphy in 196-70 years

1.Beginnings of clinical (In vivo) nuclear medicine:

Thyroid imaging with rectilinear scanner

Result: large nodal struma

16

Fields of Nuclear Medicine:

1 A. „In vivo” imaging

Hal Anger (Berkeley)with his positron camera

Developer of the scintillation camera

1957: Anger camera

Principle:

many photomultiplier tubes „see”

the same large scintillation

christal; an electronic circuit

decodes the coordinates of each

event

(„ Anger resistant matrix”)

17

Planar Gamma cameras (1970-80 )

18

Selecting the „ideal” human radionuclide :

• Should allow imaging with gamma camera:- gamma emitter- energy from 80 to 400 keV

(lower : absorbed in the patienthigher: bad detector sensitivity)

• Half time: ~ hours(shorter: difficulties with productionlonger : high patient dose)

• Should be linked to a suitablecompound.

19

Emission imaging: Study types

Static:imaging an equilibrium distribution

Dynamic:series of images following the accumulation /

metabolic pathways / secretion of a radiopharmaceutical

Whole body:static images connected

Tomographic:single photon emission computed tomography (SPECT)

positron emission tomography (PET)

20

Examples of in vivo „single photon isotope” studies:

Malignant thyroid tumour

99mTc-Pertechnetate

decreased activity with pertechnetate

increased MIBI accumulation

99mTc-MIBI

Examples of in vivo „single photon isotope” static studies

Case of Parathyroid adenoma

(More „cell specific” maps )

99mTc- fyton (organ-Cuppfer cell -specific agent)

Examples of in vivo „single photon isotope” static studies :

Nodular lesions of the liver in cirrhosis

Examples of in vivo „single photon isotope” static studies

Breast scintigraphy: 99mTc-MIBI („mitochondrial map”)

tu

Examples of in vivo „single photon isotope” static studies

Case of Pulmonary embolisation (Two lung functions re imaged.)

PERF: perfusion images with [Tc-99m] macroaggregated albumin

INH: after inhalation of [Tc-99m] DTPA aerosol

Examples of in vivo „single photon isotope” static studies

Case of lung abscess: 67Ga-citrateExamples of in vivo „single photon isotope” static studies

Static kidney : by Tc-99m DMSA (organ specific )

(in vitro 99m Tc-HMPAO labelled leucocytes- cell specific map

Examples of in vivo „single photon isotope” static studiesExample: Crohn disease in actíve stage by in vitro labelled leucocytes

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Examples of in vivo „single photon isotope” Dynamicstudies

Kidney

29

Results of normal dynamic kidney study

30

Examples of in vivo „single photon isotope” Dynamic studies

Gall bladder emptiing: reduced contractility

31

Examples of in vivo „single photon isotope” Dynamic studies

Monitor bile excretion process - from a single view- at various times

Result of

Hepatobiliary

scintigraphy

Tomographic reconstruction

1. Projections

2. Filtered backprojection

Advantages vs. CT:

- functional imaging- a wide range imaged

reslicing is possible

Drawbacks:

- poor resolution- attenuation- scatter

SPECT

33

Planar Gamma cameras and SPECTs

3434

Whole body bone scintigram by double headed SPECT

Spot images by planar

Gamma camera

Examples of in vivo „single photon isotope” static studies

Examples of in vivo „single photon isotope” static studies: SPECT

Brain perfusion SPECT (Tc-99m HM-PAO)

36

Examples of in vivo „single photon isotope” static studies: SPECT

Case:Lung tumor with 111In-Somatostatine-receptor scintigraphy

Examples of in vivo „single photon isotope” static SPECT studies:

Cardiological SPECT (Special sofwares are needed.)

Myocardium: „bull’s eye” display (polar map)Reversible defects by cardio C SPECT :

short axis slices

Cardio SPECT-Reversible defect: bull’s eye maps

40

Dual isotope study: Transaxial slice

[Tc-99m] Phytate [In-111] Octreotide Fused images

tumornormal

parenchyma

Case of Carcinoid tu. (Two cell functions framed in same time!)

4141

1. „In vivo” imaging

BB. With positron emitters (Brief history)

Principle: Two 511 keV photons resulting from annihilation

fly in opposite directions.Their coincident detection determines the line of annihilation.

• Michel M. Ter-Pogossian, Mallinckrodt Institute

• Michael E. Phelps, UCLA4242

Possibilities to Produc artificial radioactive materials

Stanley Livingstone and Ernest Lawrence with their 8 MeV cyclotron(1935)

• In nuclear reactors

(high neutron flux)

• Using accelerators(circular: cyclotron)expensive!

Ernest Lawrence(Berkeley)inventor of the cyclotron

43

PET - advantages

• Coincidence detection at 180°:- higher sensitivity- better signal/noise ratio

• Easier attenuation correction(sum of the two paths inside =body thickness)

• More physiologic radiopharmaceuticals(C-11, N-13, O-15, F-18)

*

44

The structure of PET camera

Detector system

Coincidenc circuit !!

45

3 dimensional cine display of PET study made by FDG

on dedicated PET camera (1996)

46

Functional vs. structural imaging:Case: Low-grade recidive glioma (FDG) PET+MRI fusion made by software )

PET Center,

Debrecen

Based on conventional methods: Stage I

Role of PET in oncology:Tumor staging

FDG-PET shows stage IIIS

1

2

3

4

1 2

3 4

Summed coronal slices Transaxial slices 48

Previous and recent PET , PET-CT tools

Negatív iontöltéső Ciklotron ( PET TRACE) árnyékolás nélkül

Targetkamrák

Gyorsító mágnes

Ionbevezetés helye

Praeclinical PET- SPECT

PET - CT

49

Recent trends in multimodality in vivo imaging:

2007.: start of Gemini TOF 64 slice PET-CT in Debrecen :Step forward in oncology and cardiology

PET tracers: FDG, 11C-metionin

18F-FDG TF PET-CT in mal. tumor diagnostics:

remnant of colon cancer

• Rectum tu. Lokális recidíva?

Dr. Fekésházy A. képanyaga

5118F-FDG TF PET-CT in mal. Tumor follow up) 5252

Tumor localization for targeted radiation therapy by

PET-CT

53

New trend

54

SPECT-CT Example: right suprarenal adenoma

Radiopharm.: 131I-Nor-cholesterolEgésztest vizsgálat

CT SPECT SPECT/CT

55

More special softwares for 3D volume-rendered fusion images

Protocols in the CardIQ Fusion software (a–d). The main protocols include tools

for image coregistration, epicardial contour detection,

coronary artery segmentation.56

Fields of Nuclear Medicine:

2 In vitro” concentration measurements

ROSALYN YALOW

(1921-)

1977 Nobel Laureate in Medicine

„for the development of

radioimmunoassays of peptide

hormones”

1960: Yalow and Berson developed a radioassay for

measuring Insulin concentration from plasma samples

(saturation analysis)

RIA: radioimmunoassay

(competitive protein binding;

the ligand is labeled)

IRMA: immunoradiometric assay

(„sandwich” assay)

57

In vitro isotope (RIA) lab- different tools, ecquipments (1980 )

58

Fields of Nuclear Medicine:

3. Therapy with unsealed radiactive preparations

Principle:

Beta-emitting radiopharmaceuticals go directly to the cells

or tissue to be destroyed or deactivated

Very specific radiopharmaceuticals are needed

Unsealed preparation:

One that mixes in the patients’ body on a molecular level

(e.g. after intravenous injection)

59

Radionuclide therapy

The administration of open radionuclides for therapeutical purposes. The radiopharmaceuticals get right to the cells to be destroyed, and act there locally.

Generally beta- (rarely alpha-) radiating nuclides are used, as beta radiation reaches only a small neighborhood of its source.

Most common aims of radionuclide therapy:

• Intracavital therapy (uterus, abdomin cav. Intraarticular)

• Radioimmunotherapy * • Palliative therapy of bone metastases*

• Radioiodine therapy of hyperthyreosis*• Radioiodine therapy of thyroid carcinoma metastases*

60

Exampels of Intracavital therapy-The injection of radionuclides right into some cavity

(not through the blood stream or lymphatic drains

• SynoviumIndication: Chronic synovitisMechanism: Irradiating the cells of the synovial membrane decreases fluid production.- The choice from beta-emitting radionuclides depends on the size of the synovial cavity.

• PleuraIndication: Palliative therapy in order to reduce fluid collection caused by tumors (cancers of the breast and lung, lymphoma) or inflammation.

• PeritoneumIndication: Palliative therapy in order to reduce ascites caused by tumors.(Mesothelioma, ovarian adenocc.)(Also: radioimmunotherapy )

• Intrathecal therapyIndication: Leukemia with thecal involvement Mechanism: Fagocytosis of the arachnoid membrane cells.

• CystsIndication: Cystic degeneration of a brain tumor, high risk of surgical treatment.

Colloidal radiopharmaceuticals are administered, labeled by: Rhenium-186, Erbium-169, Yttrium-90, Phosphor-32, Gold-198