Multimodality Imaging(MRI, PET, CT, etc..)

Jonathan Dyke, Ph.D.Assistant Research Professor

of Physics in RadiologyCitigroup Biomedical Imaging Center

Weill Cornell Medical College

Sackler Institute for Developmental PsychobiologySummer Lecture Series

July 9, 2009

CyclotronRadiochemistry

Cyclotron design from Ernest Lawrence’s1934 patent application.

#protons + #neutrons = Mass #

Atomic # = # protons (never changes)

Basic HS Chemistry is useful.

What does the atomic # define?

What does the atomic mass define?

Radioisotope Production

16O + p -> 18F + n8 9

Target Material: Purified Water

Production of 18F precursor to FDG

Positron Emission Tomography

“PET” Scan (“DOG” Scan)

Is a positron stuff of fiction?

e+ + e- -> a + b

Courtesy: Brookhaven National Lab

PET: Coincidence Detection

Filtered Back Projection(Key for both PET and CT!)

Courtesy: Univ British Columbia

Clinical Applications of PETAlzheimer’s Disease

Primate - 11C-Raclopride Imaging

Courtesy: Shankar Vallabhajosula, Ph.D.

18F-FDG Lymphoma Study:2-[fluorine-18] fluoro-2-deoxy-D-glucose (FDG)

11C-5-Hydroxytryptophan (5-HTP)

Image Analysis:Standard Uptake Value:

Courtesy: PET/CT in clinical practice By T. B. Lynch, James Clarke

Pre-Tx SUV=15 Post-Tx SUV=2

ComputedTomography“CAT Scan”

Creation of X-RaysCirca 1896

Circa 1900

Circa 2000

X-Ray Tube Construction

X-Ray DensitiesDo the following appear

Dark or light on an X-Ray image?

•Air•Fat

•Bone

CT Hounsfield Units

CT Hardware

Advantages:

1)CT completely eliminates the superimposition of images of structures outside the area of interest. 2) because of the inherent high-contrast resolution of CT, differences between tissues that differ in physical density by less than 1% can be distinguished. 3)data from a single CT imaging procedure consisting of either multiple contiguous or one helical scan can be viewed as images in the axial, coronal, or sagittal planes, depending on the diagnostic task. This is referred to as multiplanar reformatted imaging.

In the ED it’s FAST!

CT Diagnostic Utility:Head:

Chest:

Cardiac:

Abdominal and pelvic:

Extremities:

Trauma, Stroke, Tumor, Biopsy

Lungs, Pneumonia, Emphysema, Embolism

Coronary artery disease (High Dose)

Renal stones, appendicitis, pancreatitis, diverticulitis

Fractures, dislocations.

CT - Stroke

CT PerfusionCBF

CBV

MTTAJNR 2000;21:1441–1449.

CT Radiation DoseDiagnostic Advantage

Vs. Increased Risk Cancer

Assumes linear relationship between radiation dose and cancer risk (Controversial).

Risk for pediatric patients developing cancerfrom CT scan is greater than adults.

~ 500 in every 600,000 scans.“CT is an extremely valuable tool, and nobody should

hesitate to undergo CT when it is indicated.”

•CONTRAST ENHANCEMENTCONTRAST ENHANCEMENT•DIFFUSION IMAGINGDIFFUSION IMAGING•FAST IMAGING METHODSFAST IMAGING METHODS•FUNCTIONAL IMAGINGFUNCTIONAL IMAGING•PERFUSION IMAGINGPERFUSION IMAGING•SPECTROSCOPYSPECTROSCOPY

Advanced MRI Applications

MRI CONTRASTENHANCEMENT

Dia Weakest -1Para Weak ~10Ferro Strong ~25,000Super Strong ~5000

Magnetism of Materials

How does it affect the signal?

•What type of material is Gadolinium?•How many unpaired e- does in Gd-DTPA?•What compound do we detect the effect of contrast on?

Contrast Mechanisms Dictate Method of Studyin Magnetic Resonance Imaging

How does an agent affect relaxation times?

1 = 1 + R1,2 C

T1,2 T10,20

Solomon-Bloembergen Equations (1955)

What factors influence whether the T1 or T2 effect will dominate the MRI signal?

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% S

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Muscle/Vessel

Clinical Apps:Why are contrast agents

necessary given the excellent resolution of

un-enhanced MRI images?

When is a contrast scan prescribed?

Tumor, Stroke, AngiographyCNS disease

But.. Talk is cheap..

Nephrogenic SystemicFibrosis

MRIDIFFUSIONIMAGING

BASIC DWI PHYSICS

CLINICAL APPLICATIONS

TRACTOGRAPHY

What physical aspects or systems In nature exhibit diffusion?

What principles govern diffusion?

The “Drunken” WalkEinstein – 1905

How far does a drunk walk?<R(t)2>= 2 D t vs. R(t)=

v t

DH O= 3x10-3 mm2/sDbrain = 1x10-3 mm2/s

2

What affect does diffusion have on the MRI signal?

S=S0 e –b D

DWI Atten Brain = 1/(2.782)DWI Atten CSF = 1/(2.782^3)

How can you image diffusionat the cellular level accounting

for patient motion?

Patient motion ~ 1-2mmDiffusion length ~ 10-100m

90o

Excitation

Image

Acquisition

RF

Gx

Gy

Gz

G

180o

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Pulse Sequence: Spin-Echo Diffusion Weighting

Why the different contrastbetween a DWI & ADC image?

DWI = ADC

Clinical Apps:

Acute AML pre/post Tx*Courtesy: Doug Ballon, 2003

A.W. Song, http://www.biac.duke.edu/education/courses/fall04/fmri/

Isotropic vs. Anisotropic

Diffusion Tensor Imaging

3T MRI – NYP - Tumor

MRFUNCTIONAL

IMAGING

BOLD EFFECT PHYSICS

PHYSIOLOGICAL FACTORS

CLINICAL APPLICATIONS

Roy, C.S., and Sherrington, C.S. 1890. On the regulation of the blood supply of the brain. J. Physiol. 11:85-108. 100 years pass…..

Ogawa, S., Lee, T.M., Nayak, A.S., and Glynn, P. 1990. Oxygenation-sensitive contrast I magnetic resonance image of rodent brain at high magnetic fields. Magn. Reson. Med. 14:68-78.

•Oxyhemoglobin is diamagnetic •Deoxyhemoglobin is paramagnetic •Neuronal activity->Less deoxyhemoglobin•Less susceptibility difference between capillary vessel and brain tissue•Longer T2*•Signal increase in T2* Sequence

How big an increase are we talking about?

How does BOLD really work?

Blood Oxygen LevelDependent Signal

Source: Buxton book Ch 17

Dale & Buckner, 1997

Hemodynamic Response

Repeated Trials – Dale/Buckner 1997

Motor Activation in AFNI

Where do we expect activation?

Cortical mapping in thesurgical suite.

Neuron, 2006,18;643-653. – Courtesy BJ Casey

Clinical Apps:• Improving clinical procedures, e.g.

presurgical planning for brain tumors • Direct: Mapping of functional properties

of adjacent tissue • Indirect: Understanding of likely

consequences of a treatment• Understanding cognition • Studying brain development • Investigating brain physiology• ** Henning – Minimally Conscious

State

MR PERFUSIONIMAGING

Physiologically, what happens when a tracer enters the blood

supply?•What factors influence the distribution and kinetics?

Johns Hopkins – Dept Radiology

T1W – DCE MRIDYNAMIC CONTRAST ENHANCED IMAGING

2D Fast Spoiled Gradient Echo, 12 mm slice, 8/0 slices, TR/TE 8 ms/2 ms, 15.63 kHz RBW, 22 cm FOV, 256 x 128 matrix, 8.56 sec/resolution

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Minutes

S/S0

Pediatric Osteogenic Sarcoma: Post-Chemotherapy

Grade IV Responder: 100% Necrotic

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DCE-MRI & ANGIOGENESIS

•What role does neovasculature fill in tumor growth? (Goldman,1907)

•How far from a vessel can a tumor cell survive? (Thomlinson & Gray,1955)

•Does DCE produce any physiologically significant parameters?

Pharmacokinetic Modeling of Tracer Kinetics(Kety, 1951)

ve dCe(t) = Ktrans (Cp(t)-Ce(t))dt

Cp Cp

kep

InterstitialLesion

kelKin

k12

PlasmaIntravascular

Brix/Hoffman 2 Compartment Model

Gd-DTPA 0.1 mM/kg

Compartmental Model Fits

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Grade II - 50% Necrotic:A=0.75, kep=5.47/min, kel=0.03/min

Grade IV - 100% Necrotic: A=0.30, kep=2.79/min, kel=-0.21/min

Does this model actually fit real data?

CLINICAL APPS:•Tumors: breast, brain, bone

•Drug Trials: anti-angiogenic

•Arthritis: joint/synovium

•BBB leakage/permeability

T2*W – DSC MRIDYNAMIC SUSCEPTIBILITY

CONTRAST

Representative Perfusion Maps

MTT EPI

CBFCBV

62 year old with left MCA territorial stroke. The perfusion maps show prolonged MTT with corresponding decreased CBF and

CBV.

“Arterial Input Function”

Raw SI-ln(S/S0)

Minutes Minutes

“CT Perfusion is for wimps.”

Difficulties in MRP quantitation.•Delay

•Dispersion•Saturation Effects

•Partial Volume Effects•Susceptibility Masking

•Conversion to Concentration

Refs: van Osch,2000; Rausch,2001; Wu,2003

Cerebral Blood Volume

Cerebral Blood Flow

Mean Transit TimeMTT=CBV/CBF

Central Volume Theorem

dttAIF

dttC

h

hCBV

t

SV

LV

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)(1

1

1

)()()( tRtAIFCBFtCt

CBF (ml/100 gm/min)

Normal GM = 39+/-10.3Normal WM = 14.7+/-4.1

Ischemia < 10.0

CBV (ml/100 gm )

Normal GM = 4.4%+/-0.9Normal WM = 2.3%+/-0.4

Ischemia = >6 ml

DWI/PWI Services in Stroke: www.synarc.com

MR SPECTROSCOPY

NMR Active NucleiWhat can we see?

Raw Signal“FID”

FFT

“Chemical Shift”Electron Shielding

Water = 4.7ppmLipid = 1.3 ppm=(4.7-1.3) ppm*127.5MHz = 434 Hz @ 3.0 TeslaT=1/= 2.3 ms (IP, OOP)

NAACHOCRELAC

1H Metabolites

Lac 3 1.32 1.33 doubletPara-PyruvateCH3 1.36Alanine 3 1.47 1.44 doubletArginine 4 1.64Lys 5 1.7 1.69 multipletLeu 3 1.71 1.71 multipletLeu 4 1.71g-aminobutyric acid 3 1.89Lys 3 1.89 1.91 multipletAcetate 2 1.91 1.92 singletArginine 3 1.92Ile 3 1.97 1.96 multipletPro 4 1.99N-Acetyl CH3 2.01N-Acetyl CH3 2.05Glu 3 2.06 2.08 multipletN-Acetyl CH3 2.07 2.16 singletMet S(CH3) 2.13 2.14 singletMet 3 2.14 2.16 multipletGln 3 2.15 2.14 multiplet glutamateGSH Glu 3 2.17 GSSG Glu 3 2.17NAAG Glu 4 2.212-Hydroxy-Glutarat 2.27Val 3 2.27 2.24 multipletg-aminobutyric acid 2 2.3Glu 4 2.34 2.36 multiplet gultamatePyr 4 2.4Succinate 2.4Carnitine 2 2.452-Keto-Glutarat 2.46Gln 4 2.46 2.41 multipletCitrate 2.52 doublet B-Alanine 2 2.55GSSG Glu 4 2.55GSH Glu 4 2.57Citrate 2.62 doublet

g-aminobutyric acid 4 3.022-Keto-Glutarat 3.03Creatine CH3 3.03 3.04 singletPCreatine CH3 3.03Cn CH3 3.07phosphoethanolamine 3.15B-Alanine 3 3.18choline 3.2 singletArginine 5 3.21N(CH3)3 3.21PE (N) 3.21Cysteamine (N) 3.23phospho-choline 3.24 singletCarnitine (CH3) 3.24Glc 2B 3.25Oxal-Acetate 3.25Tau (N) 3.25 3.26 tripletPara-Pyruvate CH2 3.27Phe 3 3.27phosphatidylcholine 3.28 singletglycerophospho ethanolamine (N)3.29Inositol (myo) 5 3.29 3.28 tripletHypotau (S) 3.36Inositol (scyllo) 3.36Pro 5 3.39Glc 4a 3.41 3.40 tripletGlc 4B 3.41 3.42 tripletTau (S) 3.41 3.46 tripletGlycogen 4 3.43Glc 5B 3.44 3.47 dddCarnitine 4 3.45Glc 3B 3.5Glc 2a 3.55 3.54 ddInositol (myo) 1,3 3.55 3.56 doublet of doubletsGly 2 3.56 3.61 singletThr 2 3.58PC (N) 3.59Inositol (myo) 4,6 3.61 3.63 dd

A sampling of 1H metabolites

Ex-vivo Mouse brain perchloric acid extract @ 11.4T

What price is paid in detecting these signals?

Grade IIIGBM

Pre-Tx

Dyke JP, Sanelli PC, Voss HU, Serventi JV, Stieg PE, Schwartz TH, Ballon D,Shungu DC, Pannullo SC. Monitoring the Effects of BCNU Chemotherapy Wafers (Gliadel®) in Glioblastoma Multiforme with Proton Magnetic Resonance Spectroscopic Imaging at 3.0 Tesla. J Neurooncol. 2007 Mar;82(1):103-10.

31P Metabolites@ 3.0 Tesla