Girraj shakyaMvsc (4999)

Vet surgery and radiology

RECENT ADVANCES IN SCINTIGRAPHY RECENT ADVANCES IN SCINTIGRAPHY AND NUCLEAR IMAGINGAND NUCLEAR IMAGING

Introduction

Principle, Equipments and Radiopharmaceutical agents

Applications in Veterinary field

Miscellaneous applications

Conclusion

Future prospects

INTRODUCTION

Nuclear medicine is a branch of medicine and medical imaging that uses radioactive isotopes (radionuclides) and process of radioactive decay in the diagnosis and treatment of disease

Diagnostic branch of nuclear medicine

Nuclear imaging :

It is a generic term that cover many imaging techniques

Common theme being that ionization radiation originating with in

the body is detected and imaged in order to determine something

about the physiology or anatomy of the subject

Scintigraphy :

Involves the production of images demonstrating the distribution of

radioactive materials within a patient following the internal

administration of a radioactive pharmaceutical

PRINCIPLE

Two basic requirements :

1. A gamma ray emitting pharmaceutical that concentrates in the area of interest

2. A gamma camera (detector) to provide information or image of the pharmaceuticals distribution

Pharmaceuticals which after entry into blood stream gets localized in a particular tissue or organ

Before the injection it is labelled with a radioisotopes, thus localization of the isotopes can be detected by using gamma camera due to emission of gamma rays from the area of interest

PROCEDURE

Radiotracer Administered

Biodistribution (Space and Time)

Gamma ray emission

Gamma camera detection

Computer Image formation

Schematic presentation for a gamma camera .

Information gathered from the patient is saved as numerical data pattern

and intensity of gamma rays

Numerical data displayed as a gray-scale map in a matrix on a monitor

Ability to post-process and image manipulation

Ability to archive and transmit images easily

ONE HEAD GAMMA CAMERA TWO HEAD GAMMA CAMERA

Radiopharmaceutical Applications

99mTechnetium-MDP Bone imaging

99mTcO4 & 131Iodine Thyroid imaging

99mTc-DTPA Renal Study (GFR)

99mTc-DMSA Kidney imaging

99mTc-HMPAO Brain imaging

99mTc-HSA Lungs imaging

99mTc- Setambi Heart imaging

99mTc-HMPAO-Leucocytes Infection imaging

99mTc-RBCs Spleen

Commonly used radioisotopes for imaging

ADVANTAGES OF TECHNITIUM

• Metastable nucleoisomer

• Isometric decay

• Lower price

• Greater availability

• Faster blood clearance

• High resolution image

THYROID SCINTIGRAPHY

Thyroid scintigraphy is one of the most common nuclear medicine applications in

veterinary medicine (Balogh et al. 1998)

Recently sodium 99mTechnetium-pertechnetate (99mTcO4-) has been used more

extensively for thyroid imaging than radioiodine because of its availability, low

cost and radiation safety.

Isotope Half-life Gamma energy

99mTcO4- 6 hours 140 keV

123I 13.3 hours 159 keV131I 8 days 356 keV

Dose : 37 and 222 MBq IV for a cat or dog

99mTcO4- localizes in the thyroid glands 20-30 min after application

Ventral and lateral aspects of the neck region are imagined

routinely

Additional ventral and lateral views of the neck and thorax should

also be acquired to rule out ectopic tissue or tumor metastasis

Images are evaluated visually and quantitative analysis can be performed

Morphological data include :

location, and size of thyroid lobes are extremely important before surgical excision

Response to therapy especially when suspected malignancy is diagnosed

Quantitative data such as:

Time-activity curves of the thyroid gland ,

Radionuclide uptake of the thyroid gland

Calculated activity ratios (thyroid / salivary glands)

reveal very useful additional information for estimating the

functional status of the thyroid glands

Thyroid scintigraphy

Time-activity curves of the thyroid gland

Activity ratios of the thyroid gland, salivary glands and background

Thyroid uptake of injected dose

( Balogh et al ., 1999)

Indications

Hyperthyroid cats

Thyroid tumors in dogs

Post operative evaluation

Detection of thyroid metastasis

Congenital thyroid dysfunction

Image: 20-30 min after 80-150 MBq/0.5-1.5mL 99mTc-pertechnetate application.

Notice the differences between radiopharmaceutical concentration in thyroid

glands.

Euthyroid Hyperthyroid Hyporthyroid

• Thyroid carcinoma causing hyperthyroidism

• Notice increased uptake in the left- sided thyroid tumor and the

complete suppression of the normal right thyroid lobe.

• Thyroid scan performed on normal dog,

• Notice the 2 symmetrical thyroid lobes that are

approximately as "bright" as the dog's salivary tissue

Thyroid carcinoma with pulmonary metastasis

Unilateral thyroid adenoma Bilateral thyroid adenomaSimilar uptake

Hyperthyroid cat with a single ectopic (and intrathoracic) thyroid adenoma

HEPATIC SCINTIGRAPHY

There are 3 main forms of hepatic scintigraphy

(Wolff et al. 1988; Koblik et al. 1990)

Reticuloendithelial scintigraphy Tc labelled colloids : sulphur colloid, serum albumin microaggregates The uptake mechanism is based on phagocytic activity of the RES-cells (in the liver – Kupffer’s

cells)

Indications: Evaluating hepatic and splenic morphology (size and shape) Hepatic or Splenic masses of unknown origin (Cyst, haematoma, abscess, tumor)

Hepatobiliary scintigraphy

99m Tc IDAs (Derivatives of iminodiacetic acids )

The radiopharmaceutical is in normal cases in the liver parenchyma within 2

min, in the gall bladder between 2 and 20 min and thereafter it is excreted into

the small intestines

Indications:

Hepatobiliary scintigraphy holds for morphological and functional information

Bile excretion function of hepatocytes, biliary tract patency,

Extrahepatic biliary obstructive lesions, acute or chronic cholecystitis

• Dynamic pictures of hepatobiliary scintigraphy in a dog.

• After 80 MBq/1mL 99mTc BrIDA injection the radiopharmaceutical distributes

in the whole body, concentrates in the liver parenchyma and is excreted through

the gall bladder into the intestines

Portosystemic scintigraphy

Agents:

99m Tc –pertechnetate, 201 Thallium or 99mTc serum albumin macroaggregate

In parallel with the administration 3-4 seconds frame are acquired until 3-5 min

while the radiopharmaceutical is passing through the v.portae into the liver and

after capillarization into the heart

Indications :

Portosystemic shunt scintigraphy is a very sensitive, non-invasive screening test

for the presence of an pathological connection between portal and systemic veins

.

Schematic drawing of the normal portal circulation of

a rectally administered material. Notice that the

material is initially transported to the liver.

Normal study: Composite image of a normal dog

showing the uptake of radioactivity into the portal

vein and liver

Portosytemic Shunt: Composite image showing

uptake of the radioisotope from the rectum into the

portal vein

Notice that the dye bypasses the liver and appears in

the heart and lungs first

Reticuloendothelial : 60 min - whole liver visualized Static imaging

Hepatobiliary : Dyanamic or static frame imaging (2,10,15, 20, 25, 30, 45 and 60 min)

Portosystemic: Always rapid dynamic study . Image taken until 3-5 min (Wolf et al., 1998 and Koblik et al ., 1990)

Imaging Protocol

Renal scintigraphy

One of the earliest nuclear medicine applications in both veterinary and

human fields is renal morphologic imaging.

(Twardock et al.1991; Nemeth et al. 1998)

Radiopharmaceuticals used for this method are numerous;

99mTechnecium labelled diethylene triamine penta aceticacid (99mTc DTPA)

Glucoheptonate (99mTc GH), or

More frequently dimercaptosuccinic acid (99mTc DMSA)

Doses : range 37-185 MBq/0.5-1mL

Renal scintigraphy

Two types:

Quantitative renal imaging (morphology)

99m Tc -DTPA, 99m Tc -GH and 99m Tc -DMSA

DMSA in used in humans for detection of cortical disorders pyelonephritis

Functional renal scintigraphy 99m Tc MAG 3 10% filtered and 80% excreted by PCT

99m Tc DTPA Determination of GFR

GFR = 0.194 X (% Dose uptake Rt. & Lt. kidney) – 0.37

Nementh et al.,1998

Contd ...

Dose : 37-185 MBq IV ( avg dose 90)

Imaging varies with agent used :

99m Tc DTPA ( Few minutes)

99m Tc DMSA (Hours)

Renal morphologic study : Static images

Functional renal scintigraphy – Dynamic images are taken.

In the first minute to examine arterial blood flow of kidneys and thereafter until 20 min to evaluate renogram

Indications

Evaluate renal blood flow and function.

Evaluate for urinary tract obstruction (transit time)

Evaluate for renovascular hypertension.

Evaluate renal transplant for complications (Susan et al., 1999)

Calculate ERPF and GFR

Research purpose (anaesthetic monitiring) (Mitchell et al., 1998)

No effect of hypoproteinemia over binding

Constraints

Effect of anaesthesia

Ageing effects

Effect of drugs

Dynamic images - uptake of radionuclide by normal kidneys

Dilated right ureter Normal kidneys

Barthez et al., 2000

Poorly functional right kidney within a large perirenal cyst

Brain Scintigraphy

Planar brain scintigraphy : Functional integrity of BBB rather than morphology

Less common in human (CT and MRI)

Passive diffusion immediately after injection (95% sensitivity )

Presence after renal clearance indicates damage to BBB

Brain accumulation

6 conditions

Increased vascularity

Abnormal capillary permeability

Uninhibited pinocytosis

Adjacent capillary oedema

Increase in extracellular space of tumor

Ability of tumor cells to bind with molecules intracellularly

Brain Scintigraphy

Dorsal, lateral and caudal images taken 1-4 hrs after injection

Agents :

99m Tc DTPA

99m Tc O4ˉ

99m Tc HM-PAO

99m Tc ECD Costly, passes BBB

Dose : 370-1110 MBq (T.D)

(Dykes et al ., 1994)

Cardiac Scintigraphy Two types:

Mycardial imaging : 99m Tc MIBI, 123I MIBG or 201 Thallium

(Fujimoto et al., 2004)

Functional scintigraphy : 99m Tc autologous RBCs

Dose : 74-370 MBq/ dog or cat

Left lateral, ventral and left ventral oblique palnnar images - 20-60 min

Functional examination : Radionuclide ventriculography

First pass radionuclide angiogram

Indications

Myocardial ischemia or infraction

Ventricular function ( ejection fraction, ejection rate)

Effect of drugs (digoxin)

Congenital cardiac diseases

Fusion images from myocardial perfusion scintigraphy (MPS) and computed tomography (CT) constructed before (A) and

after (B) the coronary artery bypass grafting (CABG)

• Images of MPS with Thallium-201 showed the improvement in myocardial ischemia

of the anterior wall (black arrow head). • The grafts, the left internal thoracic artery (LITA) to the left anterior descending

artery

(LAD) and the radial artery (RA) to the diagonal branch (Dx), were shown to be

patent with CT. RCA, right coronary artery; LCX, left circumflex artery; and SVG,

saphenous vein graft.

To visualise the irrigation capacities of the heart muscle during an exercise.

The living areas of the muscle are coloured red whereas the dead zones are coloured blue or green

All red or orange areas are normal, whereas the yellow or blue areas do not

have enough blood.

Note that some areas of the heart appear yellow, whereas they were red during

rest.

Pulmonary scintigraphyTwo types

Ventilation: 133, 127 Xenon, 81 m Krypton or 99m Tc DTPA

Perfusion : 99m Tc labelled macroaggregate serum ablumin (99m Tc MAA)

Dose : 20-150 MBq/dog or cat

555-740 MBq/horse

Static images are taken of ventral , dorsal and lateral thorax after 2-5 min

Indications:

Ventillation study : Research purpose

Perfusion study : PTE, COPD , heart worm or EIPH(Harnagle et al ., 1987)

Pleural effusion

Pleural effusionPleural effusion along with hyperthyroidism

Broome , 1993

Other applications of pulmonary scintigraphy

Study of the regional lung function (Votion et al., 1999)

Imaging of pulmonary infection and/or inflammation

Chronic and diffuse inflammation (67Ga) and acute inflammatory lesion (labelled WBCs) (Chianelli et al., 1997)

Inflammatory cell involvement in lung diseases

To determine the role of specific inflammatory cells in the pathogenesis of respiratory disorders and for investigating the effect of anti-inflammatory drugs on inflammatory cell recruitment into the lung s (Ussov et al., 1999)

Alveolar-capillary barrier integrity Imaging of lung cancers (Chiti et al., 1999)

Aerosol deposition studies (Wilson, 1998)

Gastro intestinal scintigraphy

Radionuclide studies of gastric emptying and motility are the most physiologic studies available for studying gastric motor function

The study is noninvasive, uses a physiologic meal (solids with/without liquids)

Scintigraphic assessment of gastric emptying in a healthy dog Fifteen minutes after feeding of a radioactively-labeled meal, radioactivity can only be observed in the stomach As time passes, the radioactively-labeled food moves into the small intestine and after 6 hours, there is only a small amount of radioactivity detectable in the stomach

scintigraphy is performed in patients suspected of active gastrointestinal bleeding

using Tc-99m labeled red blood cells (RBCs)

Bleeding site in right colon

(Terdiman et al., 1997

Dynamic anterior abdominal images are acquired at a frame rate of 10–60 sec / frame over a 60 to 90 min period

GIT bleeding

BONE SCINTIGRAPHY

Bone scintigraphy seems to be the most frequently performed veterinary nuclear

medicine procedure (Lamb 1991; Chambers 1996)

99mTc methylene diphosphonate (99mTc MDP) most commonly used one

Dose ranges10-20 Megabecquerel(MBq) / Bwt in kg

The skeletal scintigraphic examination can be divided into three imaging phases

(3-phase bone scintigraphy)

Vascular phase or blood flow phase or nuclear angiogram (phase I),

Extracellular or soft tissue phase (phase II),

Bone phase (phase III)

phase I

The first phase imaging is showing larger blood vessels (both arteries and veins)

Phase I imaging is a sensitive test for loss of vascularity

(e.g.: ischemic injury, vascular infarction),

Acute inflammatory processes where significant local capillary recruitment has

occurred (e.g. in acute localized cellulitis).

Phase II

The images represent the radiopharmaceutical bio-distribution in the ECF space of

all body tissues after delivery via the vascular system

Phase II imaging is useful in detecting and evaluating inflammatory diseases in

soft tissues surrounding the skeleton

(e.g. in tendon or ligament injuries, synovitis, myositis)

Phase III

The radiopharmaceutical localizes in bone on the surface of the exposed hydroxy-

apatite crystals while the remaining radiopharmaceutical is excreted via the urinary

tract

Phase III imaging detects and evaluates acute or chronic bone disease

(e.g. in complete or incomplete fractures,

osteoarthritis,

osteomyelitis,

periosteal reactions,

Primary or metastatic malignancies

Advantage :

scintigraphy is able to detect abnormalities at a very early stage: a few hours after

injury incomplete bone fractures can be detected scintigraphically

Whole-body imaging of a dog having osteosarcoma. Notice the very clear radiopharmaceutical uptake in the left knee. No metastases are seen anywhere else in the body

The dog was injected 370 MBq/0.5mL 99mTc MDP two hours before investigation.

Oncological scintigraphy

Detecting malignancies : 99mTc MIBI, 99m Tc DMSA and 99m Tc MoAbs

(Balogh et al., 1997 )

Extent of invasios (Infln. foci) : 99m Tc HM-PAO,111 Indium oxine & 99m Tc IgG

(Tucker et al., 1989)

Dose : 100-740 MBq/dog

Static imaging or whole body examinations are performed 2, 4,6 hours or later Dorsal, ventral and left lateral image taken

Multiple delayed images with diffuse metastatic disease

Intestinal lesions

AVMI, 1999

Malignancy detection

Cervical LN metastasis

Additional diagnostic value of fused SPECT and CT images in assessing possible bone

metastases.

A. Transverse SPECT image show bilateral foci of increased tracer uptake in thorasic vertebra

B. Transverse CT image shows no apparent bone lesion.

C. Transverse fused image shows precise localization of abnormal tracer uptake in articular

facets of head of rib (arrows)

A. Coronal SPECT image show increased tracer uptake in the lumbar vertebral bodyB. Coronal reformatted CT image shows compression fracture in third lumbar vertebral bodyC. Coronal fused image shows precise localization of abnormal tracer uptake in end plate of 3rd lumbar vertebral body

Splenic sequestration scintigraphy (Berry 1996)

Lymphoscintigraphy (Daniel andBailey

1996)

Gastrointestinal motility (Voges et al. 1996)

Mucociliary transport (Whaley et al. 1987)

Sperm motility (Balogh et al. 1995)

Bleeding detection (Metcalf 1987)

Miscellaneous applications

Disadvantages of Scintigraphy High cost of radiopharmaceutical agent

Strict safety precaution required

Non-specificity to the etiology

Poor intrinsic anatomical resolution

Complementing with other diagnostics is challenging

Difficult interpretation and prognosis

Dosages need to be standardized for different species

Trained staff needed

Conclusions

Reliable technique

Most sensitive (????)

In naive phase in our country

Cost limit its application in animals

Radioactive hazards are comparable

What has to be achieved in future?

Useful in diagnosis where conventional methods fails

Making technique available at affordable rates

Collaboration with medical science

Employment generation