Tecnicas de Medicina

Nuclear

Bases y fundamentos

Procedimiento de obtención de imágenes médicas

Gammagrafía

Tomografia Computarizada por Emision de Fotones

Simples (SPECT)

Tomografía por Emisión de Positrones . PET

Aprender conceptos básicos sobre cómo se generan

las imágenes de Medicina Nuclear: gammagrafías,

SPECT y PET

La Medicina Nuclear (MN) utiliza sustancias

radiactivas: isótopos (iso = igual; topos = lugar)

Fines: diagnósticos, terapéuticos y de

investigación.

Estas sustancias radiactivas (radionúclidos o

trazadores) se introducen (in vivo) en la parte

del cuerpo que se quiere estudiar y se hace la

imagen detectando la radiación que emite.

Es mínimamente invasiva (inyección).

Es una técnica funcional: no estudia la

anatomía sino su funcionamiento.

Abarca en la practica, la totalidad del

organismo.

El nivel de radiación es similar al de

otras técnicas radiológicas (ej. RX)

Radionúclido Energía

(keV)

T(1/2) Estudios

99mTc131I

67Ga133Xe201Tl

140

364

39

81

30-140

6 horas

8´04 días

3´25 días

5´3 días

72 horas

Cerebro, tiroides, riñón, pulmón

Tiroides y riñon

Tumores y abscesos

Pulmón

Estudios cardíacos

INTRODUCCIÓN

Algunos de los elementos más usados en MN:

Fines diagnósticos:

Renograma isotópico de un

paciente con HTA

secundaria, que muestra una

atrofia renal derecha

Imágenes de Medicina nuclear

normales.

Diferencias (MN, rayos X):

•MN usa radiación gamma ():

Energías Frecuencias

MN: [104 - 107 eV] [1019 - 1022 Hz] Rayos X: [10 - 104 eV] [1015 - 1019 Hz]

•En MN la fuente de radiación es interna (en el interior del

cuerpo del paciente), en rayos X es externa.

•Trazador con radiofármaco: permite obtener una representación

morfológica o información funcional o dinámica. (En rayos X

contraste)

INTRODUCCIÓN

Esquema básico de un sistema de

IMN

Sustanciaradiactiva

órganoseleccionado

Radiación

Cristal decentelleo

Analizadorde amplitud

Contador deimpulsos

Gammagrafía

Colimador

Tubofotomultiplicador

Imágenes en Medicina Nuclear

Uso de Rx, radionucleidos y de

radiofarmacos en obtención de imágenes

Con las imagnes de Medicina Nuclear pueden observarse procesos fisiologicos,

como asimismo de Estructuras anatomicas.

En estas tecnicas se inyectan en los pacientes por via

Intravenosa, drogas radiactivas (Radiofarmacos) que emiten rayos gamma

Una vez que son captados por el tejido, organo o sistema de interes.

La cantidad de radionucleidos inyectados, se encuentran en el orden de

concentraciones

de nano a picomolar, de manera de disminuir los riesgos para los pacientes

Durante el estudio de los procesos fisiologicos delos mismos.

El semiperiodo fisico de estos materiales radiactivos es de solo unos pocos

Minutos a semanas. The time course of the

process being studied and the radiation dose to the target are

considered. The nuclear camera then, in effect, takes a time-exposure

"photograph" of the pharmaceutical as it enters and concentrates in

these tissues or organs. By tracing this blood flow activity, the

resulting nuclear medicine image tells physicians about the biological

activity of the organ or the vascular system that nourishes it. Nuclear

Medicine has a wide variety of uses, including the diagnosis of cancer,

studying heart disease, circulatory problems, detecting kidney

malfunction, and other abnormalities in veins, tissues and organs.

Medicina Nuclear: camara gamma

O N NH COOEt EtOOC

99mTc

S S

Aplicacion: perfusion cerebral

Radiofarmacos

Imagen nuclear de

Cuerpo completo

SPECT esta basada en una tecnica convencional de imagenes nucleares

Y usando ademas la tecnica y metodos de reconstruccion tomografica.

SPECT: single photon emission

computerized tomography

Collimator

NaI(Ti)

crystal

PMT

a

b c

d

Electronics

X

Y

Counts/pixel

Resolución Espacial – Es la medida del grado de detalles provistos por la

imagen final reconstruida y por lo tanto del tamaño de lesiones que

potencialmente pueden ser detectadas. En otras palabras: cual es el grado

de detalle en el cual puede ser Observada una imagen o cuanto puede ser

resuelta o separada.

Sensibilidad, tiempo muerto – describe de que manera y con que eficiencia

se Detectan los decaimientos radiactivos y la distribucion del trazador, para

Formar finalmente la imagen.

Una fuente isotropica irradia en forma igual hacia todas las direcciones del

espacio. Los detectores, recolectan parte del total de los decaimientos,

dentro de un angulo Solido limitado por los colimadores.

Algunos de estos eventos se pierden debido a que el sistema necesita de

un tiempo de procesamiento entre la deteccion de un evento y el siguiente.

(dead time o Tiempo Muerto).

Características de Rendimiento de los

sistemas de imágenes de Medicina Nuclear

Signal to Noise ratio (SNR) - The relative strength of the information

and the noise. If the lesion is small compared with the spatial resolution

the contrast is reduced because the high lesion activity blurred into the

neighborhood by the detector response.

Uniformity, Linearity - The image of an object should be independent

of its position in the field of view. This is not true in real systems.

This can be assessed in calibration measurements to derive correction

factors. This reduces non-uniformity from 10% to 3%.

The conventional nuclear medicine imaging process.

Typical radionuclides used are 140 KeV Tc-99m and 70 KeV photons

from Tl-201.

The gamma ray photons emitted from the radiopharmaceutical

penetrate through the patient body and are detected by a set of

collimated radiation detectors. The emitted photon experience

interaction within the body by the photoelectric effect which stops

their emergence from the body or compton scattering which

transfers part of the energy to free electrons and the photon is

scattered into a new direction. These photons are also detected

by the camera and cause blurring of the image if un-treated with

image reconstruction and processing tools.

Pixel I

Activity ai

Intersected area fi

r

P(r,q)

q

In 2-D tomographic imaging, the 1D detector array rotates around

the object distribution f(x,y) and collects projection data from various

projection angles q. The integral transform of the object distribution

to its projections is given by:

Ç

Which is called the Radon transform. The goal of image

reconstruction is to solve the inverse Radon transform. The solution

is the constructed image estimate f(x,y) of the object distribution

f(x,y).

The measured projection data can be written as the integral of

radioactivity along the projection rays.

p t c I x y dst' ( , ) exp[ ( , ) ]q

z0

The measured projection data can be written as the integral of

radioactivity along the projection rays.

In SPECT attenuation coefficient is not so important, so it can

be considered as constant in the body region under inspection.

l(x,y) is the pathlength between the point (x,y) and the edge of the

attenuator (or patient’s body) along the direction of the projection

ray.

The image reconstruction problem is further complicated by the non

stationary properties of the collimator detector and scatter response

functions and their dependence on the size and composition of the

patient’s body.

p t c x y dse( , ) ( , )q

z

p t c x y l x y dse( , ) ( , ) exp[ ( , )]q

z

Cristal de centelleo (Yoduro de sodio con talio-INa(Ta))

Transductor de energía en energía luminosa.

El cristal está acoplado a un conjunto de fotomultiplicadores de sección exagonal.

Transductor de energía luminosa en electrones. Salida del fotomultiplicador: impulsos eléctricos amplitud proporcional a la energía de la

radiación

y número proporcional a la actividad del elemento radiactivo en el punto analizado.

Llevando estas señales a un circuito de posicionamiento, obtenemos las coordenadas X e Y, que indican la posición donde se ha detectado

el fotón.

C

PROCEDIMIENTO DE OBTENCIÓN DE IMÁGENES MÉDICAS

Colimador tipo pinhole.

La imagen es invertida y el

tamaño dependiente dela

distancia al plano objeto.

Colimadores de múltiples

orificios paralelos, convergentes y divergentes

PROCEDIMIENTO DE OBTENCIÓN DE IMÁGENES MÉDICAS

Gammagrafía

SPECT

PET

Es la técnica mas simple.

Su funcionamiento es similar al de las radiografías, una sola imagen por volumen.

Varios tipos dependiendo de la zona: › Osea (tumores de hueso)

› Pulmonar (trombos en las arterias pulmonares)

› Tiroidea (nódulos en la tiroides)

› Renal (función de los riñones)

Gammagrafía de un

adenoma suprarrenal

causante de hipertensión

arterial secundaria

Renograma isotópico de un

paciente con HTA secundaria,

que muestra una clara atrofia

renal derecha. La pequeña

cantidad de contraste isotópico

que se observa ha llegado por

vía del pedículo suprarrenal.

Gammacámara que puede realizar movimientos de rotación alrededor del cuerpo del paciente o anillo.

Imagen de la distribución del trazador en 3D utilizando la combinación de imágenes obtenidas desde diversas orientaciones. Pueden obtenerse imágenes de cortes axiales, sagitales, coronales.

Mediante los algoritmos de retroproyección, similares a los TC, se puede reconstruir la imagen.

Ejemplo de un escáner de SPECT

Detectores de

radiación

Positrón

fotón

fotón

Detección de positrones mediante dos gammacámaras

Tipos de cámaras PET:

a) un par

b) un anillo hexagonal giratorio alrededor del paciente

c) Anillo circular que rodea al paciente

PET generates images depicting the

distributions of positron-emitting nuclides in

patients

In the typical scanner, several rings of

detectors surround the patient

PET scanners use annihilation coincidence

detection (ACD) instead of collimation to

obtain projections of the activity distribution

in the subject

Positrons emitted in matter lose most of their

kinetic energy by causing ionization and

excitation

When a positron has lost most of its kinetic

energy, it interacts with an electron by

annihilation

The entire mass of the electron-positron pair

is converted into two 511-keV photons,

which are emitted in nearly opposite

directions

If both annihilation photons interact with

detectors, the annihilation occurred close

to the line connecting the two interactions

Circuitry within the scanner identifies

interactions occurring at nearly the same

time, a process called annihilation

coincidence detection

Circuitry of the scanner then determines the

line in space connecting the locations of

the two detector interactions

ACD establishes the trajectories of the

detected photons, a function performed by

collimation in SPECT systems

Much less wasteful of photons than

collimation

Avoids degradation of spatial resolution

with distance from the detector that occurs

when collimation is used to form projection

images

A true coincidence is the simultaneous interaction of emissions resulting from a single nuclear transformation

A random coincidence, which mimics a true coincidence, occurs when emissions from different nuclear transformations interact simultaneously with the detectors

A scatter coincidence occurs when one or both of the photons from a single annihilation are scattered, but both are detected

Scintillation crystals coupled to PMTs are

used as detectors in PET

Signals from PMTs are processed in pulse

mode to create signals identifying the

position, deposited energy, and time of

each interaction

Energy signal is used for energy

discrimination to reduce mispositioned

events due to scatter and the time signal is

used for coincidence detection

Early PET scanners coupled each

scintillation crystal to a single PMT

› Size of individual crystal largely determined

spatial resolution of the system

Modern designs couple larger crystals to

more than one PMT

Relative magnitudes of the signals from the

PMTs coupled to a single crystal used to

determine the position of the interaction in

the crystal

Material must emit light very promptly to

permit true coincident interactions to be

distinguished from random coincidences

and to minimize dead-time count losses

at high interaction rates

Must have high linear attenuation

coefficient for 511-keV photons in order

to maximize counting efficiency

Most PET systems use crystals of bismuth germanate (Bi4Ge3O12, abbreviated BGO) › Light output 12% to 14% that of NaI(Tl), but

greater density and average atomic number give it higher efficiency at detecting 511-keV photons

Other inorganic scintillators being investigated: lutetium oxyorthosilicate and gadolinium oxyorthosilicate – faster light emission than BGO produces better performance at high interaction rates

Energy signals sent to energy discrimination

circuits which can reject events in which

the deposited energy differs significantly

from 511 keV to reduce effect of photon

scatter in patient

Energy window may be adjusted to include

part of the Compton continuum, increasing

sensitivity but also increasing the number of

scattered photons detected

Time signals of interactions not rejected by the energy discrimination circuits are used for coincidence detection

When a coincidence is detected, the circuitry or computer of the scanner determines a line in space connecting the two interactions › PET system collects data for all projections

simultaneously

Projection data used to produce transverse images of the radionuclide distribution as in x-ray CT or SPECT

In 2D (slice) data acquisition, coincidences are detected and recorded within each detector ring or small groups of adjacent detector rings

PET scanners designed for 2D data acquisition have thin annular collimators (typically tungsten) to prevent most radiation emitted by activity outside a transaxial slice from reaching the detector ring for that slice

Fraction of scatter coincidences reduced because of the geometry

Coincidences within one or more pairs of

adjacent detector rings may be added to

improve sensitivity

Data from each pair of detector rings are

added to that of the slice midway between

the two rings

Increasing the number of adjacent rings

used in 2D acquisition reduces the axial

spatial resolution

In 3D (volume) data acquisition, axial

collimators are not used and

coincidences are detected between

many or all detector rings

Greatly increases the number of true

coincidences detected; may permit

smaller activities to be administered to

patients

For the same administered activity, the increased interaction rate increases random coincidence fraction and dead-time count losses › 3D acquisition may require less activity to be

administered

Scatter coincidence fraction is much larger and number of interactions from activity outside the FOV is increased › Activity outside the FOV causes few true

coincidences, but increases rate of random coincidences and dead-time count losses

3D acquisition may be most useful in low-

scatter studies, such as pediatric and

brain studies

Some PET systems are equipped with

retractable axial collimators, permitting

them to perform 2D or 3D acquisition

For 2D data acquisition, image reconstruction methods are similar to SPECT

For 3D data acquisition, special 3D analytic or iterative reconstruction techniques are required

In PET, the correction for nonuniform attenuation can be applied to the projection data before reconstruction; in SPECT, the correction for nonuniform attenuation is intertwined with and complicates the reconstruction process

Whole-body PET systems achieve a spatial

resolution slightly better than 5 mm FWHM in the center of the detector ring

Spatial resolution limited by:

a) intrinsic spatial resolution of detectors

b) distance traveled by positrons before annihilation

c) the fact that annihilation photons are not emitted in

exactly opposite directions from each other

Intrinsic resolution of detectors most significant

Spatial resolution of PET is best in the center

of the detector ring and decreases slightly

with distance from the center

This occurs because of detector thickness

and inability to determine the depth in the

crystal where an interaction occurs

Uncertainty in depth of interaction causes

uncertainty in the line of response for

annihilation photons that strike the

detectors obliquely

Distance traveled by positron before annihilation also degrades the spatial resolution

Distance is determined by maximal positron energy of the radionuclide and density of the tissue

Radionuclide that emits lower energy positrons yields superior resolution

Activity in denser tissue yields higher resolution than activity in less dense tissue

Although positrons lose nearly all of their

momentum before annihilation, the positron

and electron possess some residual

momentum when they annihilate

Conservation of momentum predicts that

the resultant photons will not be emitted in

exactly opposite directions

This causes a small loss of resolution, which

increases with the diameter of the detector

ring

Point source of positron-emitting radionuclide in air

midway between two identical detectors

True coincidence rate is

where A is the activity of the source, G is the

geometric efficiency of either detector, and is the

intrinsic efficiency of either detector

Because the rate of true coincidences detected is

proportional to the square of the intrinsic efficiency,

maximizing the intrinsic efficiency is very important

22 AGRT

Differs in PET from SPECT, because both

annihilation photons must escape the

patient to cause a coincidence event to

be registered

Probability of both photons escaping the

patient without interaction is the product

of the probabilities of each escaping:

) ) ) dxdx eee

For a 20-cm path in soft tissue, the chance

of both annihilation photons of a pair

escaping the tissue without interacting is

about 15%

Attenuation causes a loss of information

and, because the loss is not the same for all

lines of response, causes artifacts in the

reconstructed transverse images

Loss of information also contributes to

statistical noise in the images

Some PET systems provide one or more retractable positron-emitting sources to measure the transmission of annihilation photons through the patient › Gamma-ray emitting source (Cs-137) may be

used

Sources revolve around the patient so attenuation is measured along all lines of response through the patient

Attenuation correction cannot compensate for increased statistical noise; increases imaging time

SPECT with high-energy collimators or

multihead SPECT cameras with

coincidence detection capability

› Less acceptable for brain imaging or evaluation

and staging of neoplasms

Dedicated PET systems that are less

expensive than those with full rings of BGO

detectors, but which provide better

coincidence detection sensitivity than

double-head scintillation cameras

PET scanner more efficient than scintillation camera due to use of annihilation coincidence detection instead of collimation; also yields superior spatial resolution

Spatial resolution in SPECT deteriorates from edge toward center; PET is relatively constant across transaxial image, best at center

Attenuation less severe in SPECT; accurate attenuation correction possible in PET (with transmission source)

Cost: SPECT ~US$500,000; PET ~US$1M - $2M

Main factors limiting availability of PET are

the relatively high cost of a dedicated PET

scanner and, in many areas, the lack of

local sources of F-18 FDG

Multihead SPECT cameras with coincidence

circuitry and SPECT cameras with high-

energy collimators provide less expensive,

although less accurate, alternatives for

imaging FDG

PET enables physicians to assess chemical or physiological changes

related to metabolism. Since the origins of many diseases are

biochemical in nature, these functional changes often predate or exceed

structural change in tissue or organs. PET imaging utilizes a variety of

radiopharmaceuticals, called "tracers," to obtain images. PET tracers

mimic the natural sugars, water, proteins, and oxygen found in our

bodies. These tracers are injected into a patient and collect in various

tissues and organs. The PET system takes a time-exposure of the tracer

and generates a "photo" of cellular biological activities. PET images

can be used to measure many processes, including sugar metabolism,

blood flow and perfusion, receptor-ligand binding rates, oxygen

utilization and a long list of other vital physiological activities.

PET scanning uses artificial

radioactive tracers and

radionuclides. Their lifetime is

usually rather short, thus they

need to be produced on site.

Some examples of such materials are:

Radionuclide Half life Application Carbon-11 20.3 min Positron emitter for metabolism studies

Copper –64 12.8 hours clinical diagnostic agent for cancer and

metabolic disorder

Iodine –122 3.76 min Positron emitter for blood flow study

Iodine –131 8.1 days Diagnose thyroid disorders including cancer

Iron - 52 8.2 hours Iron tracer for PET bone marrow imaging

Nitrogen – 13 9.9 min Positron emitter used as 13NH for heart

perfusion studies

Strontium – 85 64 days Study of bone formation metabolism

Oxygen – 15 123 sec Positron emitter used for blood flow

Technetium – 99m 6 hours The most widely used radiopharmaceutical

In nuclear medicine

PET has a million fold sensitivity advantage over MRI in tracer study

and its chemical specificity, PET is used to study neuroreceptors in

the brain and other body tissues. It is efficient in the nanomolar range

where much of the receptor proteins in the body. Clinical studies

include tumors of the brain, breast, lung, lower GI tract. Additional

study of Alzheimer’s disease, Parkinson’s disease, epilepsy and

coronary artery disease affecting heart muscle metabolism and flow.

PET studies has immeasurably added to the understanding of oxygen

utilization and metabolic changes that accompany disease.

PET imaging starts with the injection of metabolically active tracer – a biologic

molecule that carries with it a positron emitting isotope. Over a few minutes the

isotope accumulates in an area of the body for which the molecule has an affinity.

i.e. glucose labeled with 11C or glucose analogue labeled with 18F, accumulates in the

brain or tumors, where glucose is used as the primary source of energy. The

radioactive nuclei then decay by positron emission. In positron (positive electron) ,

a nuclear proton changes into a positive electron and a neutron. The atom maintains

its atomic mass but decreases its atomic number by 1. The ejected positron combines

with an electron almost instantaneously, and these 2 particles undergo the process of

annihilation. The energy associated with the masses of the positron and electron

particles is 12.022MeV in accordance with E=MC2 . This energy is divided equally

between 2 photons which fly away from one another at 1800 angle. Each photon has

an energy of 511 keV. These high energy gamma rays emerge from the body in

opposite directions and recorded simultaneously by pair of detectors.

The annihilation event that gave rise to them must have occurred somewhere

along the line connecting the detectors. Of course if one of the photons is scattered,

then the line of coincidence will be incorrect. After 100,000 or more annihilation

events are detected, the distribution of the positron-emitting tracer is calculated by

tomographic reconstruction procedures. PET reconstructs a 2 dimensional image

from the one dimensional projections seen at different angles. 3-D reconstructions

can be done using 2D projections from multiple angles.

Tungsten

septum

Scintillator

Lead

shield

P P

N

+

-

Positron annihilation

photons (1800

0.250)

Tagged

metabolic

activity

11C nucleus

Detector crystal width

Anger logic

Photon noncolinarity

Positron range

Reconstruction algorithm

Acquisition

Calibration data

Correction data

Reconstruction

Sinogram

Counts/ray

Image

SA reconstructed slices

• Blood volumes

• Oxygen consumption

• Perfusion

• Glucose consumption

CENTELLEADOR

FOTOMULTIPLICADOR

ELECTRÓNICA

2 RAYOS γ

COLINEALES

RADIOISÓTOPOS

β+ DE

VIDA CORTA

CICLOTRÓN

Radioisótopos

β+

Reconstrucción

de la

Imagen

Radioisótopo

+

Trazador

Inyección

al

Paciente

Decaimiento β+

y Aniquilación (2γ)

Detección

de

Coincidencias

IMAGEN FUNCIONAL:

DISTRIBUCIÓN DEL TRAZADOR

EN EL ORGANISMO

APLICACIONES:

-DETECCIÓN DE TUMORES

- FUNCIÓN CEREBRAL

-EFICIENCIA DEL DETECTOR

- SENSIBILIDAD DEL SISTEMA

- RESOLUCIÓN TEMPORAL

- RITMO DE RECUENTO

- RESOLUCIÓN ESPACIAL

Punto

Paralelepípedo

Esfera

¿Dentro

de Esfera?

Rayo

Θ,φ

Intersección

Detectores-Rayo

Detector

¿Dentro

de

planos?

Numeración

Detectores

Guardar datos

n veces

No

Sí

No

Sí

PROGRAMA DE

SIMULACIÓN

MÉTODO

MONTECARLO

Datos

DETECTOR IDEAL

2γ COLINEALES LOR

EJE X

EJE Y

EJE X EJE Y

π/3

π/3

x

φ

y

F1

F2

υx

υy

υxr

υxr

EQUIVALENTES

dxpedxWedyxf r

xi

rxx

xi

x

rrx

rr

rrx

r

0

22),()(),(

f(x,y)

φ

xr

0

0

xr

φ

dxdyxysenxyxfxP rr )cos(),(),(

Transformada de Radon

PROYECCIÓN RETROPROYECCIÓN

Δφ

Δυxr

Sobremuestreo en el

origen de frecuencias

υx

υy

υ 0

Filtro rampa

Ventana Hamming

Tipos de Filtros

)2cos( rN x

p(xr,φ)

xr xr

p·cos

φ

υxr

xr

(x, z)

1

2

2

3

4

5

5

4

3

1

2

dxpedxWedyxf r

xi

rxx

xi

x

rrx

rr

rrx

r

0

22),()(),(

xr = x·cosφ +y·senφ

6 mm 4 mm 3 mm

FWHM ≈ 3 mm

φ (rad)

xr (cm)

CORREGIDA

POR

NORMALIZACIÓN

φ (rad)

xr (cm)

CORREGIDA

POR

NORMALIZACIÓN

CONCLUSIONES:

- Reconstrucción de Imágenes con FBP en

Modo 2D.

- Estudios Realizados: Resolución,

Normalización, Filtros.

- Simulación de la Emisión y Detección de

Gammas en P.E.T.

Imágenes PET de un cerebro activo en varios estados, tras inyección intravenosa de 18F, con deoxy-glucosa. (de Shung-92)

Low Pet Scan of Patient.

The Positron Emission Tomography

Lab at Mount Sinai Medical

Center is located in New York City.

We are dedicated to the study of

Alzheimers, Schizophrenia and

general questions regarding how

the brain changes with age. This

research is accomplished through

the co-registration of PET and MRI

modalities. We have developed

software in order to better aid in

this research

http://neurosurgery.mgh.harvard.edu/pet-hp.htm

Parkinson's Disease

http://neurosurgery.mgh.harvard.edu/pet-hp.htm

Huntington's disease

Sitio caliente: sala de preparación de

radiofármacos

Sala de pacientes

Sala de exploraciones

Sala de almacenamiento de residuos

radiactivos

Equipo humano: Especialista y técnico