Principle of Neurobioimaging

Peni K Samsuria MutalibMedical Physics Department

Faculty of Medicine Universitas Indonesia

Goal

• Describe the principle of X-Ray, T-Ray, CT-scan, NMR (MRI), PET, STED

• (Principle of USG)

18961901

In 1901 Wilhelm Konrad Roentgen: the first recipient of the Nobel Prize for Physics

1896 his wife’s hand, he made the first X-ray photo, and thus, made it possible to look inside the human body without surgical intervention.

X-ray vs. T-ray!!droidmill.com

T-Ray

worldsfamousphotos.com

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There are 2 kind of Image• Anatomical (Gross)

– Tumor: Ventriculography,pneumoencephalography– Injury– Angiography

• Functional– Alzheimer STED 2014 Noble Prize– Cognitive psychology: Thought identification, Mind

reading (higher metabolism area & “light up” on scan

Brain CT with and without contrastSource: X-Ray

Without Contrast: directWith Contrast:• Only one CT contrast study

should be scheduled within a 48 hour period.

• BUN & Creatinine must be done within 72 hours of the scan.

• Nothing to eat, but clear liquid after midnight before the scan.

cedars-sinai.edu

CT scanning of the head is typically used to detect:

                                             

•Bone abnormalities •Brain mass/tumor •Fluid collection, such as an abcess •Hemorrhage •Hydrocephalus •Ischemic process, such as a stroke •Trauma or fracture of the skull

Look at the ventricles!

Normal CT

http://www.seattlechildrens.org/medical-conditions/brain-nervous-system-mental-conditions/hydrocephalus/

Brain CT!!Blood vessels: brightly w contrast

The bones are whiter than the surrounding area. (Whiter means higher attenuation.)

Blood vessels also brightly due to the injection of an iodine-based contrast agent. Displaced Ventricles in

Brain CT

Typical scan dosesExamination Typical effective dose

(mSv)(milli rem)

Chest X-ray 0.1 10

Head CT 1.5 150

Screening mammography 3 300

Abdomen CT 5.3 530

Chest CT 5.8 580

Chest, Abdomen and Pelvis CT 9.9 990

CT colonography (virtual colonoscopy)

3.6 - 8.8 360 - 880

Cardiac CT angiogram 6.7-13 670 - 1300

Barium enema 15 1500

Neonatal abdominal CT 20 2000

For comparison, survivors of the atomic bombings of Hiroshima and Nagasaki were exposed to an average of 40 mSv of radiation. This dose is comparable to 2-3 extensive CT scans, and can increase the risk of cancer.

Mod from Brenner NEJM rev 2007

Brain tumor MRI

With contrast

fMRI of the Brain

1. Magnetic resonance (MR) imaging uses radio waves and a strong magnetic field = NMR Nuclear Magnetic Resonance

2. Functional magnetic resonance imaging (fMRI) is used to measure metabolic changes in an active part of the brain (speech, sensation, memory, thought) etc.

3. Injuries and disease, such as stroke or brain tumor, cause functions to shift to other parts of the brain.

This 3 principles is used for planning surgery, radiation therapy, treatment for cerebral vascular or other interventions.

FMRI vs. fMRI?

The term "Functional MRI" (with a "capital F") can also include other MRI techniques that are sensitive to physiologic changes (such as changes in water motion)- EEG-PET.

FMRI identifying, investigating, and monitoring brain tumors, cerebral vascular, and certain chronic disorders (multiple sclerosis, dementia or seizures.

FMRI

And "little f" fMRI usually refers to mapping of brain activity using MRI.

fMRI studies are often used in planning brain surgery, since they can help physicians monitor normal brain function as well as any disturbed brain function (cerebral vascular, trauma, or degenerative disease (such as Alzheimer's) on brain function.

EEG MRI PET

FMRI: MRI & PET Brain

MRI, PET and CT scans of the brains of people affected by (clockwise from top left): Alcoholism, marijuana use, multiple sclerosis, cocaine use, Parkinson's disease, Alzehemier's disease.

11C contrast MRI & PET

Typical MRI and PET brain images of [11C]NNC112 (a) and [11C]FLB457 in the conscious MR images were (1.5 T). PET images were generated by summation of image data from 37 to 64 min after injection

FDG 18F Fluorodeoxyglucose (Fludeoxyglucose) make by cyclotron

18F-FDG or FDG

The meaning of:

What is Radio frequency, X-Ray and Gamma-ray?

• Geometrical Optics

• Physical Optics

• Quantum Optics

Electromagnetic wave spectrum: Radio waves!

(From Hopkins Ultraviolet Telescope Project, http://praxis.pha.jhu.edu/.)

Geometrical optics• Deals with those optical phenomena that are

mostly easily described with straight lines and plane geometry.

• Deals with macroscopic light

Physical optics• Dealing with the wave nature of light, • Deals with electromagnetic wave

Quantum optics• Dealing with quantum aspects of light, • Deals with particle (light as photon)

Optics

The experiments of all of the various known properties of light may be

grouped together and classified under one of the three following heads:

Geometrical Optics

Physical Optics Quantum Optics

Rectilinear propagation

Diffraction Photo-electric effect

Finite velocity Interference Compton effect

Reflection Polarization Atomic excitation

Refraction Double Refraction Pair production

X-ray and CT Scan: Absorption, Transmision Black-grey-white• 1895: Roentgen • 1900’s: Tomography (Y: tomos=slice)• 1970: CTScan (Computerized Tomography) X-ray or

CAT, PET 1975, MRI 1984• Nowadays imaging: CTScan, USG, MRI, PET, fMRI

USG BrainBaby’s brain USG Acranial & anencephaliy

Basic principle of Tomography• Collimated-X-raysbody

through the detector which measure the transmited intensity.

• Severals points was measured, while source and detector were move together pass through the body.

• This instrument is turned little surrounded the body’s axis and once again scanned; many times with interval (may be) 1o for 180o.

Rangkaian

detectors

X-ray source

CT Scan: source X-Ray

• Transmitted Intensity light from many points at any scan, and any angle, were sent to computer which reconstruct the slice image.

• Slice which will be imaging is cut to many small figure (pixel)

• Any pixel represent the intensity of the transmitted light and give a nuance of graded grey and e.g. image from elemen 100 x 100 for total 10 4 pixel ( 100 detector from 100 different angles.

Several mathematic reconstruction technique

• Iteration tech.

• Fourier transformation tech.

• Reverse projection tech. more directly

Nuclear Magnetic Resonance (NMR) = Magnetic Resonance Imaging

(MRI) of the Head

• Uses a magnetic field and pulses of radio wave energy for source. In many cases an MRI provides information that cannot be obtained from an X-ray, ultrasound, or CT scan.

• The MRI can also detect tissue damage or disease, such as infection, inflammation, or a tumor.

NMR/MRI for Medical Area (2003)

• MRS: Magnetic Resonance Spectroscopy for 1) determine the structure of unknown chemical stuff and 2) to study the binding characteristic of a known compound

• MRI: Magnetic Resonance Imaging to make a image af ‘slices organ

• NMR: Nuclear Magnetic Resonance is a basic of MRS dan MRI

MRI/NMR merupakan emmision (pemancaran/pencurahan) imaging

MRI

Patient in strength magnetic field (> 1.5 T) were given energy pulse short frequency of radio wave radio signal images which recorded from 3:

1) density of proton (H nucleus),

2) relaxation constant,

3) blood flow pattern (oxy vs. deoxy Hb)

MRI Use strong magnetic field •heart pacemaker •artificial heart valve•catheter •IUD •any metal plates, pins, screws or surgical staples•Tattoos •Eyeliner •Tooth fillings•Braces•hairpins, jewelry, eyeglasses,•hearing aids

Prepare the procedure!

Oxy vs. deoxy Hb

• The principle of fMRI imaging is to take a series of images of the brain in quick succession and to statistically analyze the images for differences among them.

• Oxy hemoglobin and deoxyhemoglobin are magnetically different is exploited. Oxy Hemoglobin shows up better on MRI images than deoxyhemoglobin; thus, oxygenated blood shows up better. Brain areas with more blood flow have been shown to have better visibility on MRI images (Cohen & Bookheimer, 1994)

correlated with brain activation• Other fMRI methods exploit the fact that the bulk movement of

hydrogen nuclei causes changes in the MRI image CSF flow, blood flow, or diffusion of water through tissue.

•When the frequency of the pulsed radio beam matches the frequency of the hydrogen atom, which induces the protons to flip, this is called the ‘Resonance Frequency’•Resonance in NMR is caused by the absorption of EM radiation in the radio frequency, by protons in magnetic field (Ho) which then flip. Flip only happen when the radio wave frequency is suitable. With strength Ho, the frequency must be more higher (E>)

•Flipped proton is also called resonanced proton

•When unflipped, there are E that emmited (signal for detector) computerized curve

Resonance proton: Flip & Relaxation [Absorption & Emmission]

Radio wave absorbed by nuclear atom (proton/H+)

• 1945: Proton through ‘nuclear spin’ absorb radio wave from suitable radio frequency while places in a strength magnetic field.

• The resonance frequency from nuclear atom is depends not only on: 1) magnetic power and 2) atomic type, but also on 3) chemical atom of the environment.

• ‘Nuclear spins’ from various nucleus could be interfere each other, produce fine structures that is sejumlah puncak dalam spektrum NMR

U Ssample

Radio frequence Generator

Radio frequence Detector

Main part of NMR spectrometer NMR

Jodoh tiap signal NMR dengan proton dalam makromolekul

• = ‘sequential assignment

1985 Wüthrich: Jarak antara sejumlah besar inti hidrogen dan memakai informasi ini dengan metode matematik bedasarkan geometri jarak untuk menghitung struktur 3D untuk molekul. Saat ini 15-20% dari ribuan struktur protein telah ditentukan dg NMR. Yg lain dg kristalografi sinar-X, beberapa dg difraksi elektron atau difraksi neutron

PET (Positron Emission Tomography)

• Radioactive

• Cyclotron to make Positron emitter

• Gamma detector

Positron a pair of gamma rays

• Positrons emitted by the nuclide annihilate with atomic electrons and emit a pair of gamma rays moving in opposite directions.

• the head is surrounded by gamma detectors, the delay between a gamma ray arriving on one side and its partner arriving opposite is used to calculate the position of the decay.

• In this way a map of decays taking place in the brain can be built up. If the subject is given different stimuli-music or speech for example-the pattern of blood flow in the brain changes

http://www.corbisimages.com/stock-photo/rights-managed/42-21818506/pet-scans-show-brains-response-to-musical

PET scans showing the varying rates of activity in different parts of the brains of three people listening too music indicates the greatest activity. The technique shows how untrained listeners react to music more with the right, intuitive hemisphere of the brain, white trained musicians rely on the left, logical side of the brain.

PET with musical stimulation

http://neurostudyclub.mcgill.ca/feb2004/feb2004_p6.htm

Anterior Speech Area on PET combined with MRI by Denise Klein & Brenda Milner

Music listener vs. maestro

PET scans showing the varying rates of activity in different parts of the brains of three peoples listening to musics. Red indicates the greatest activity. The technique shows how untrained listeners react to music more with the right, intuitive hemisphere of the brain, while trained musicians rely on the left, logical side of the brain.

The PET scanner

• PET is a technique that is revolutionizing research into the activity of the brain. A patient inhales CO containing some carbon-11 isotopes. CO is very good at attaching itself to haemoglobin molecules in red blood cells.

• When areas of the brain are active the blood flow to them increases, so the concentration of carbon-11 in that part of the brain increases. The 11C isotope of carbon is artificial and decays by β+ (positron) emission.

Detector-scintillation counter-photomultiplier tubes

• Within about 1 mm of its emission point a positron will annihilate with an electron to produce two gamma-ray photons. As the positrons are not moving that quickly when they annihilate with an electron, the two photons emerge virtually back-to back, which concerves momentum.

• The patient is surrounded by a ring of scintillation counters which detect the emerging gamma-ray photons (scintillation counters are photomultiplier tubes, each with its own sodium iodide crystals)

Record the activity, but..

• PET scan activity in the speech centre of the brain

• One disadvantage of the technique is that it cannot record the activity of parts of the brain that are constantly active – only changes in blood flow can be detected.

USG (ultrasonography)

• Not an electromagnetic wave

• A mechanical wave

• Reflection not transmission and emission

USG: Lower freq for deeper

2 64 108 1412 16 18MHz

Deeper structure

Superficial structure

Higher resolutionLower resolution

HIFU: 0,25-2 MHz

ESWL: 1-3 Hzprocoagulant5-12 MHz

USG for diagnosis is a reflection imaging

• Non-electromagnetic wave imaging

• Ultrasonic wave is reflected to body interface with difference acoustic impedance medium density and for x velocity use

Sound• Gelombang EM dengan frekuensi < frek cah • (f cah 4-7.5 x 10 14 Hz) = 4-7,5 x 10 –7 m (c=.f)• Jangkauan pendengaran manusia F audio 20-20.000 Hz

(satuan frek- 1Hz=1 siklus/det) (infrasonik< 20 Hz, ultrasonik > 20.000 Hz) Ultrasonik =/= supersonik ( v>vbunyi)

Jangkauan pendenganran orang tua < 10.000 Hz

Anjing: 50.000 Hz +, kelelawar 100.000 Hz +.

AM (Amplitudo Modulasi): 530-1600 kHz,

FM (Freq Modulasi) 88MHz & 108 MHz),

TV Amerika : 54& 88 MHz untuk kanal 2-6,

174 & 216 MHz untuk kanal 7-13,

470 890 MHz: untuk stasiun (UHF: Ultra High Frequency)

Untuk membahas gerak getaran perlu definisi

• Simpangan: jarak x massa dari titik seimbang pada setiap saat

• Amplitudo (A): simpangan maksimum• Siklus: gerak bolak balik yang lengkap dari titik

awal kemudian kembali ke titik yang sama• Periode (T): waktu yang dibutuhkan untuk 1

siklus lengkap (T tak tergantung A)• Frekuensi: jumlah siklus per detik

f

Af=1/T T=1/f Bila f= 5 siklus per detik;

T=1/5 detik

f

Ultrasound (frek > 20 kHz): tak bisa didengar & difraksi kecil (tak menyebar) shg bd > kecil dpt

dideteksi

Pantulan bunyi digunakan dalam banyak aplikasi untuk menentukan jarak Sonar atau teknik pulsa-gema digunakan untuk mencari (refleksi) atau memecah benda di bawah air (batu ginjal-interferensi).

Analisa gel yg terpantul dari berbagai struktur dan batas lapisan di dalam Bumi menghasilkan pola karakteristik yg berguna utk eksplorasi minyak dan mineral.

Dinding perut

Transduser Pulsa

Gema Gema

Tulang belakangK

ekua

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a

Scan-A:

Waktu sebanding jarak rambatan

Scan-B:

Kecerahan=kekuatan sinyal

Waktu

USG menggantikan operasi pencarian dan prosedur lain yg

• Beresiko• Menyakitkan• Mahal

• Efek lain hingga saat ini – (sinar-x, laser, gelombang mikro berefek samping)

Difraksi (penyebaran) berkas sinar membatasi ketajaman citra

Cara bunyi terpantul =/= sinar x (digunakan dg prinsip abs, transmisi) CT Scan

Doppler Effects

Dg menggunakan pergeseran Doppler dari USG, digunakan utk mengukur velocity dlm tbh man, seperti aliran darah dan detak jantung janin

MCA : Middle Cerebral Artery in Transcranial Doppler

ARRS, 2004

STED Microscopy

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Lyman, Balmer, Paschen, Brackett, Pfund Series: Excitation-Emission

Nanocrystal Semiconductor

Invitrogen.com

Resonance pos & neg http://www.nature.com/srep/2013/130423/srep01707/fig_tab/srep01707_F1.html